CN112029737A - Method for enhancing function of adeno-associated virus vector - Google Patents

Abstract

The present invention provides a method for correcting singletons in selected adeno-associated virus (AAV) sequences to increase packaging yield, transduction efficiency, and/or gene transfer efficiency of the selected AAV. The method comprises altering one or more singletons in the parental AAV capsid to align them with amino acids at corresponding positions in the functional AAV capsid sequences used for alignment.

Description

Method for enhancing function of adeno-associated virus vector

The application is a divisional application of an invention patent application of international application PCT/US2006/013375, international application date 2006, 4/7/2006, Chinese national phase application No. 200680010566.6, entitled "method for enhancing adeno-associated virus vector function".

Background

Adeno-associated virus (AAV), a member of the parvoviridae (Parvovirus) family, is a small, non-enveloped, icosahedral virus with a single-stranded linear DNA genome of 4.7 kilobases (kb) to 6 kb. Since the virus is found as a contaminant of purified adenovirus stocks, AAV is designated as a dependent virus (dependently). The life cycle of AAV includes a latent phase (AAV genome site-specifically integrates into the host chromosome after infection), and an infectious phase (following infection with adenovirus or herpes simplex virus, the integrated genome is then rescued, replicated, and packaged into the infected virus). The properties of non-pathogenicity, broad host range (including non-dividing cells), infectivity, and potential site-specific chromosomal integration make AAV an attractive tool for gene transfer.

AAV vectors have been described for use as vehicles for therapeutic and immunogenic molecules. To date, several well-characterized distinct AAVs have been isolated from human or non-human primates (NHPs).

Recently, a large number of AAV of different sequences have been described by researchers [ G.Gao et al, Proc Natl Acad Sci USA, 100(10): 6081-; US-2003-0138772-A1 (24/7/2003) ], and these AAV were characterized as distinct serotypes and clades [ G.Gao et al, J.Virol., 78(12):6381-6388 (6/2004); international patent publication No. WO 2005/033321 ]. It has been reported that different AAVs exhibit different transfection efficiencies and also exhibit tropism for different cells or tissues.

It is desirable to have AAV-based constructs for the delivery of heterologous molecules to different cell types.

Summary of The Invention

The present invention provides a method for improving non-functional and/or weak AAV vectors.

In one aspect, the method provides a method of correcting singletons in selected adeno-associated virus (AAV) sequences to increase packaging yield, transduction efficiency, and/or gene transfer efficiency of the selected AAV. The method comprises altering one or more singletons in a parental AAV capsid to align the singletons with amino acids at corresponding positions in the functional AAV capsid sequences being aligned.

In another aspect, the invention provides modified AAV sequences, i.e., sequences from which one or more singletons are removed.

In yet another aspect, the invention provides an AAV vector having an AAV capsid modified according to the invention.

The following detailed description readily presents other aspects and advantages of the present invention.

Brief Description of Drawings

Figure 1 shows in vitro 293 transduction of AAV vectors corrected for singleton mutations. The correction of singleton mutations (if present) is indicated after the vector name and the numbers indicate the number of mutations.

FIGS. 2A-2C show AAV vectors assayed in 293 cells over a range of multiplicity of infection of 10¹To 10⁴Wherein figure 2A compares parental rh.8 and singleton corrected rh.8(rh.8r), figure 2B compares parental rh.37 and modified rh.37, and figure 2C compares AAV2 and AAV 8. As a control, the results of similar titrations of AAV2 and AAV2/8eGFP expression vectors are also given. The Y-axis represents the percentage (%) of eGFP positive cells as determined by flow cytometry.

FIG. 3 is a phylogenetic tree of AAV sequences showing their phylogenetic relationship and the clades to which they belong.

FIGS. 4A-4L are alignments of capsid protein (vp1) nucleic acid sequences of AAV2[ SEQ ID NO:7], cy.5[ SEQ ID NO:8], rh.10[ SEQ ID NO:9], rh.13[ SEQ ID NO:10], AAV1[ SEQ ID NO:11], AAV3[ SEQ ID NO:12], AAV6[ SEQ ID NO:13], AAV7[ SEQ ID NO:14], AAV8[ SEQ ID NO:15], hu.13[ SEQ ID NO:16], hu.26[ SEQ ID NO:17], hu.37[ SEQ ID NO:18], hu.53[ SEQ ID NO:19], rh.39[ SEQ ID NO:20], rh.43[ SEQ ID NO:21], and rh.46[ SEQ ID NO:22 ].

FIGS. 5A-5D are alignments of capsid protein (vp1) amino acid sequences of AAV2[ SEQ ID NO:23], cy.5[ SEQ ID NO:24], rh.10[ SEQ ID NO:25], rh.13[ SEQ ID NO:26], AAV1[ SEQ ID NO:27], AAV3[ SEQ ID NO:28], AAV6[ SEQ ID NO:29], AAV7[ SEQ ID NO:30], AAV8[ SEQ ID NO:31], hu.13[ SEQ ID NO:32], hu.26[ SEQ ID NO:33], hu.37[ SEQ ID NO:34], hu.53[ SEQ ID NO:35], rh.39[ SEQ ID NO:36], rh.43[ SEQ ID NO:37], and rh.46[ SEQ ID NO:38 ].

FIGS. 6A-6B are alignments of the amino acid sequences of the capsid proteins (vp1) of rh.13[ SEQ ID NO:26], rh.2[ SEQ ID NO:39], rh.8[ SEQ ID NO:41], hu.29[ SEQ ID NO:42] and rh.64[ SEQ ID NO:43 ].

Detailed Description

The present invention provides a method for improving the function of an AAV vector. The invention is particularly suited for improving packaging yield, transduction efficiency, and/or gene transfer efficiency of AAV vectors comprising one or more singletons of mutations in the capsid. The invention further provides novel AAV capsid sequences identified and prepared according to the methods of the invention.

The terms "comprises/comprising" and "including" as used in this specification and claims include other elements, values, steps, and the like. Rather, the term "consists of and variations thereof do not include other components, elements, values, steps, and the like.

Simplex mutation method of the present invention

The term "singleton" as used herein refers to a variable amino acid at a given position in a selected (i.e., parental) AAV capsid sequence. The presence of variable amino acids is determined by aligning the parental AAV capsid sequences with a library of functional AAV capsid sequences. The sequences are then analyzed to determine all such variable amino acid sequences in the parental AAV capsid: AAV sequences in functional AAV libraries are fully conserved at this amino acid position. The parental AAV sequence is then altered to change the singleton mutation to the conserved amino acid at that site in the identified functional AAV capsid sequence. According to the invention, the parental AAV sequences may have 1-6, 1-5, 1-4, 1-3, or 2 singletons. Parental AAV sequences may also have more than 6 singletons.

Once modified, the modified AAV capsid can be used to construct an AAV vector having the modified capsid. The vectors may be constructed using techniques well known to those skilled in the art.

The AAV selected for modification according to the methods of the invention is an AAV which is intended to enhance one or more of the following three functional properties, namely: packaging into a virion with a capsid of the selected AAV sequence, improves transduction efficiency or increases gene transfer efficiency. For example, a parental AAV may be characterized by a lower packaging efficiency compared to other closely related AAV. In another example, the parental AAV may have a lower transduction efficiency than a closely related AAV. In another example, the parental AAV may have a lower gene transfer efficiency (i.e., a lower ability to deliver the target molecule in vivo) as compared to a closely related AAV. In other examples, the parental AAV is qualified for each of the above functions, but one or more of the functions are to be further enhanced.

Thus, the present invention provides a library of functional AAVs in which the sequences of the AVV are aligned with the selected (parental) AAV. Suitably, the library comprises AAVs having the desired function, which is the improvement to be achieved in the selected parental AAV. In other words, each sequence of the functional AAV library is characterized by a target level of packaging capacity, a target level of in vitro transduction efficiency, or a target level of in vivo gene transfer efficiency (i.e., the ability to deliver to a selected target tissue or cell in a subject). The functional AAVs making up the library may each have one, two or all of these functional characteristics. Other functions of interest for the library can be readily determined by one skilled in the art.

In one embodiment, the functional AAV is an AAV capable of producing virions with equal or greater packaging and transduction efficiencies than AAV1, AAV2, AAV7, AAV8, or AAV 9. Function can be assessed using pseudotyped setting (pseudotyped setting) with AAV2 rep and AAV2 ITRs. Thus, conventional techniques may be usedAn altered parental AAV is constructed, and an AAV vector is considered functional if the titer of virus produced by the parental AAV is at least 50% when compared to the production of AAV 2. In addition, one skilled in the art can readily determine the ability of an AAV to transduce a cell. For example, the parental AAV may be constructed to contain a marker gene for ease of virus detection. For example, AAV is made to contain eGFP or another gene that can be detected fluorescently. If the AAV comprises CMV-eGFP, the virus produced when the altered parental AAV capsid infects a multiplicity of 10⁴When 293 cells were transduced, which were pretreated with wild type human adenovirus type 5 at a multiplicity of infection of 20 for 2 hours, transduction efficiencies greater than 5% of the GFP fluorescence of all cells were functional.

Suitably, the library consists of at least three or at least four functional AAV capsid sequences representing at least two different clades. Preferably, the library comprises at least two sequences of each representative clade. In certain embodiments three, four, five, six or more clades are provided.

"clade" refers to a group of AAVs that are phylogenetically related to each other based on alignment of the AAV vp1 amino acid sequences, as determined by a adjacency algorithm, with a Bootstrap value (Bootstrap value) of at least 75% (at least 1000 replications), and a poisson correction distance of no greater than 0.05.

The literature contains a detailed description of the Neighbor-joining algorithm. See, for example: nei and s.kumar, Molecular Evolution and phylogenetics (oxford university press, new york (2000)). There are computer programs available for executing the algorithm. For example, the MEGA v2.1 program performs a modified Nci-Goiobori method. Using these techniques and computer programs, and the AAV vp1 capsid protein sequences, one skilled in the art can readily determine whether a selected AAV is contained within one clade identified herein, within another clade, or outside of these clades.

Although the clades are primarily based on naturally occurring AAV vp1 capsids, they are not limited to naturally occurring AAV. Clades may include non-naturally occurring AAVs including, but not limited to, recombinant, modified or altered, chimeric, hybrid, synthetic, artificial, i.e., other AVVs, as long as these are phylogenetically related to each other based on alignment of the AAV vp1 amino acid sequences, determined with a adjacency algorithm (bootstrap value of at least 75% (at least 1000 replications)), and a poisson corrected distance measurement of no more than 0.05.

The AAV clades described include clade a (represented by AAV1 and AAV 6), clade B (represented by AAV2), clade C (represented by AAV2-AAV3 hybrid), clade D (represented by AAV 7), clade E (represented by AAV 8), and clade F (represented by human AAV 9). These clades are represented by respective members-one of the known AAV serotypes. The known AAV1 and AAV6 belong to the same clade (clade A), and 4 isolates recovered from 3 persons are included. The known AAV3 and AAV5 serotypes differ significantly from each other, but were not detected in the screens described herein, and were not included in these clades.

Further discussion of AAV clades can be found in G.Gao et al, J.Virol, 78(12), 6381-6388 (6.2004) and International patent publication Nos. WO 2004/028817 and WO 2005/033321. The latter document also provides novel human AAV sequences, which are incorporated herein by reference.

In one embodiment, the library used in the methods of the invention does not include AAV 5. In another embodiment, the library used in the methods of the invention does not include AAV 4. However, in certain embodiments, for example: when the parental AAV is similar to AAV5, it may be desirable to include this sequence in the alignment.

Although libraries containing the smallest number of sequences can be constructed, the efficiency of identifying single mutations can be optimized by using libraries containing more sequences. Suitably, the library comprises a minimum of four sequences, representing at least two clades. Preferably, each clade in the library has at least two representative sequences. In one embodiment, the library comprises more than 100 AAV sequences. In another embodiment, the library comprises at least 3 to 100 AAV sequences. In yet another embodiment, the library comprises at least 6 to 50 AAV sequences.

AAV suitable for use in the functional libraries of the invention comprise, for example: AAV1, AAV2, AAV6, AAV7, AAV8, AAV9 and other described sequences, [ g.gao et al, Proc natl.acad sci., 100(10):6081-6086 (5/13/2003); international patent publication nos. WO 2004/042397 and WO 2005/033321) ]. Other AAVs can be readily selected by those skilled in the art, for example: AAV isolated using the methods described in International patent publication No. WO 03/093460A1 (11/13/2003) and U.S. patent application publication No. 2003-0138772A1 (24/7/2003).

According to the invention, the at least three sequences within the library are at least 85% identical over the full length alignment of the capsid sequences.

"percent (%) identity" of the amino acid sequence of the full length of the protein or a fragment thereof can be easily determined. Suitably, the fragment is at least about 8 amino acids in length, and may be up to about 700 amino acids in length. In general, when referring to "identity", "homology" or "similarity" between two different adeno-associated viruses, "identity", "homology" or "similarity" is determined with reference to sequences that are "aligned". "aligned" sequences or "alignment" refers to polynucleotide sequences or protein (amino acid) sequences that typically contain corrections for deletions or additions of bases or amino acids as compared to a reference sequence.

The alignment can be performed using a variety of well known or commercially available multiple sequence alignment programs. Programs for amino acid sequence alignment are for example: "Clustal X", "MAP", "PIMA", "MSA", "BLOCKER", "MEME" and "Match-Box" programs. Typically, these programs are used in default settings, although one skilled in the art can change the settings as desired. Alternatively, other algorithms and computer programs that can be used to derive an identity statement or to perform an alignment as described above can be used by those skilled in the art. See, for example: thomson et al, Nucl. acids. Res., "comprehensive comparison of multiple sequence alignments (A comprehensive comparison of multiple sequence alignments)," 27(13): 2682-.

There are also multiple sequence alignment programs for nucleic acid sequences. Examples of such programs include web-worn suits over the internet"W string (Clustal W)", which is available to the server, "CAP sequence component", "MAP", and "MEME". Other sources of these procedures are known to those skilled in the art. Alternatively, a Vector NTI utility may be used. There are also a number of algorithms known in the art that can be used to measure nucleotide sequence identity, including those included in the above-described programs. As another example, Fasta, a program in GCG version 6.1, can be used^TMTo compare polynucleotide sequences. Fasta^TMAlignments and percent sequence identity for the best overlap region between query and search sequences can be derived. For example, Fasta can be used with default parameters (word length 6 and NOPAM coefficients for the scoring matrix) provided in GCG version 6.1^TMTo determine the percent sequence identity between nucleic acid sequences, which is incorporated herein by reference.

According to the invention, target or parental AAV capsid sequences suspected of containing a singleton mutation are compared to the library AAV capsid sequences. This comparison was performed using a full-length vp1 protein sequence alignment of AAV capsids.

When the AAV sequences are aligned, a singleton mutation is identified for a selected amino acid position if all AAV in the library have identical amino acid residues therein (i.e., are fully conserved) and the parental AAV has different amino acid residues therefrom.

Typically, when aligned based on the AAV capsid vp1 protein, the alignment comprises insertions and deletions so determined as compared to a reference AAV sequence (e.g., AAV2), and the numbering of the amino acid residues is based on the reference scale (reference scale) generated by the alignment. However, any given AAV sequence may have fewer than dry amino acid residues than the benchmark scale. In the present invention, the terms "identical site" or "corresponding site" when describing the sequences of a parental AAV and a reference library refer to the amino acids at the same numbered residues within the amino acids of each sequence, relative to a benchmark scale used for alignment. However, outside of the alignment, these amino acids within each AAV vp1 protein may be at different numbered residues.

Alternatively, the methods of the invention can be performed using nucleic acid alignments and identifying codons encoding different amino acids (i.e., non-synonymous codons) as singleton mutations. When the nucleic acid sequence of a given codon in the parental AAV differs from the sequence of that codon in the library, but encodes the same amino acid, these different codon sequences are synonymous codons rather than singletons.

According to the invention, a parental AAV containing a singleton mutation is altered such that the singleton residue is replaced with a conserved amino acid residue of the AAV in the library.

The above substitutions of codons for variable amino acids can be made using conventional site-directed mutagenesis techniques. In general, site-directed mutagenesis, which includes only the necessary steps, is used to obtain the desired codons for conserved amino acid residues. Such methods are known to those of skill in the art and can be carried out using published methods and/or commercially available kits (e.g., available from Stratagene and Promega). Site-directed mutagenesis can be performed on AAV genomic sequences. For convenience, vectors (e.g., plasmid backbones) can be used to carry AAV sequences. Alternatively, the parental AAV may be altered by one skilled in the art using other techniques known in the art.

The parental AAV may have more than one singleton mutation, for example: two, three, four, five, six or more. However, it is possible that an improvement in function is observed after correction of one singleton mutation. In embodiments where the parental AAV carries multiple singletons, one singleton at a time may be altered, followed by determining whether the modified AAV is most functionally functional. Alternatively, it can be determined whether the desired function is enhanced after changing multiple singletons.

When the parental AAV comprises multiple singletons, even if an improvement in function is observed after the first singleton is changed, the function can be optimized by changing the remaining singletons.

Generally, parental AAVs altered in one or more singletons according to the methods of the invention are tested for function by packaging the AAV into AAV particles. These methods are well known to those skilled in the art, see, for example: g.gao et al, Proc Natl Acad sci, cited above; sambrook et al, molecular cloning: a Laboratory Manual (Molecular Cloning: A Laboratory Manual), Cold spring harbor Press (Cold spring harbor, New York).

These altered AAVs have a novel capsid produced according to the methods of the invention and are tested for their function. Suitable methods for determining AAV function are described herein, including, for example: production of deoxyribonuclease (DNAse) protects particle capacity, in vitro cell transduction efficiency, and/or in vivo gene transfer. Suitably, the altered AAV of the invention has a sufficient number of singleton mutations altered to enhance one or all of these characteristic functions as compared to the function of the parental AAV.

Novel AAV of the present invention

The invention further provides methods for predicting whether a novel AAV is functional. The method comprises using the singleton method of the invention and identifying a deletion of a singleton in a selected AAV sequence, i.e., an AAV that has no singleton.

Thus, in one embodiment, the invention provides a method of selecting an AAV for use in generating a vector. The method comprises selecting a parental AAV capsid sequence to be analyzed and identifying a deletion of a singleton mutation on the parental AAV capsid in an alignment of the parental AAV capsid sequence and a library of functional AAV capsid sequences. Once it is determined that the selected AAV capsid has no singleton mutation, the AVV can be used to generate vectors according to known techniques.

The terms "substantial homology" or "substantial similarity", when used with respect to a nucleic acid or fragment thereof, means that at least about 95% to 99% of the aligned sequences have nucleotide sequence identity when optimally aligned with another nucleic acid (or the complementary strand thereof) including appropriate nucleotide insertions or deletions. Preferably, the homology is present over the full-length sequence, or an open reading frame thereof, or other suitable fragment of at least 15 nucleotides in length. Examples of suitable fragments are described herein.

As used herein with respect to nucleic acid sequences, the terms "sequence identity", "percent sequence identity" or "percent identity" refer to the residues of two sequences being identical in the best matched alignment. The length of the sequence identity comparison may be the full length of the genome, the full length of the gene coding sequence, or a fragment requiring at least about 500 to 5000 nucleotides. However, identity between smaller fragments may also be required, e.g., fragments of at least about 9 nucleotides, typically at least about 20 to 24 nucleotides, at least about 28 to 32 nucleotides, at least about 36 or more nucleotides.

The term "substantial homology" or "substantial similarity", when used in describing amino acids or fragments thereof, means that at least about 95% to 99% of the compared sequences have amino acid sequence identity, and in certain embodiments about 97% of the compared sequences have identity, when optimally aligned with another amino acid (or its complementary strand) that contains an appropriate amino acid insertion or deletion. Preferably, the homology is over the full length sequence, or a protein thereof (e.g., cap protein, rep protein) or a fragment thereof of at least 8 amino acids, or more desirably at least 15 amino acids in length. Examples of suitable fragments are described herein.

The term "highly conserved" means at least 80% identity, preferably at least 90% identity, more preferably more than 97% identity. Identity can be readily determined by one skilled in the art based on algorithms and procedures known in the art.

The term "serotype" refers to a serological distinction between AAV having a capsid and other AAV serotypes. Serological distinction was determined based on the absence of cross-reactivity of antibodies to this AAV with other AVVs. Cross-reactivity is typically determined using a neutralizing antibody assay. To perform this assay, polyclonal sera against a particular AAV are generated in rabbits or other suitable animal models using adeno-associated virus. In this assay, antisera to a particular AAV are then tested for the ability to neutralize the same (homologous) or heterologous AAV. The dilution at which 50% neutralization was achieved was taken as the neutralizing antibody titer. Two vectors are considered to be the same serotype if the reciprocal of the quotient of the heterologous titer divided by the homologous titer is less than 16 for both AAVs. Conversely, if the reciprocal of the ratio of the heterologous titer to the homologous titer is 16 or greater, the two AAVs are considered to be different serotypes.

In additional embodiments, the invention provides AAV having novel capsids, including rh.20, rh.32/33, rh.39, rh.46, rh.73, and rh.74. The sequence of rh.20 has the amino acid sequence of SEQ ID NO. 1 or a sequence with 95-99% identity to the full length SEQ ID NO. 1. The capsid of rh.32/33 has the amino acid sequence of SEQ ID NO. 2 or a sequence with 95-99% identity to full length SEQ ID NO. 2. The capsid of rh.39 has the amino acid sequence of SEQ ID NO. 3 or a sequence with 95-99% identity to full length SEQ ID NO. 3. The capsid of rh.46 has the amino acid sequence of SEQ ID NO. 4 or a sequence 95-99% identical to full length SEQ ID NO. 4. The capsid of rh.73 has the amino acid sequence of SEQ ID NO. 5 or a sequence with 95-99% identity to full length SEQ ID NO. 5. The capsid of rh.74 has the amino acid sequence of SEQ ID NO 6 or a sequence 95-99% identical to the full length SEQ ID NO 6. Preferably, these novel AAV capsid sequences are identical to the extent that they do not have any singleton mutations. The new AAV sequence is shown in the sequence table.

In yet another embodiment, the novel AAV sequences of the present invention include singleton-corrected AAV capsid proteins and sequences encoding these capsid proteins. Examples of suitable singleton-corrected AAV sequences include AAV6.1, AAV6.2, aav6.1.2, rh.8r, rh.48.1, rh.48.2, rh.48.1.2, hu.44r1, hu.44r2, hu.44r3, hu.29r, ch.5r1, rh.67, rh.54, hu.48r1, hu.48r2, and hu.48r3. For example, singleton-corrected AAV6, including AAV6.1, AAV6.2, and AAV6.12, showed significant functional improvements compared to the parental AAV6 sequence.

Particularly desirable proteins include AAV capsid proteins encoded by nucleotide sequences identified as described above. The AAV capsid is composed of three proteins, vp1, vp2, and vp3, which are splice variants of each other. Other desirable fragments of the capsid protein include constant and variable regions located between hypervariable regions (HVRs). Other desirable fragments of the capsid protein include the HVRs themselves.

An algorithm developed to determine the regions of sequence discrimination in AAV2 resulted in 12 hypervariable regions (HVRs), 5 of which overlapped or were part of the four previously described variable regions (Chiorini et al, J.Virol., 73:1309-19 (1999); Rutledge et al, J.Virol., 72: 309-319). Using this algorithm and/or the alignment techniques described herein, HVRs of new AAV serotypes were determined. For example, HVRs are located at the following positions: HVR1, aa 146-152; HVR2, aa 182-186; HVR3, aa 262-264; HVR4, aa 381-383; HVR5, aa 450-474; HVR6, aa 490-495; HVR7, aa 500-504; HVR8, aa 514-522; HVR9, aa 534-555; HVR10, aa 581-594; HVR11, aa 658-667; and HVR12, aa705-719[ the numbering system is based on alignment using AAV2 vp1 as a reference point ]. The corresponding fragments of the novel AAV capsids of the invention can be readily determined by one skilled in the art using the Clustal X program and its default settings, or using other commercially available or well-known alignment programs and their default settings (such as those described herein) for the alignments herein.

Suitably, the fragment is at least 8 amino acids in length. However, fragments of other desired lengths may also be conveniently employed. Such fragments may be produced by recombinant or other suitable methods, such as chemical synthesis.

The invention further provides additional AAV sequences identified using the sequence information provided herein. For example, in view of the sequences provided herein, genome walking technology (Siebert et al, 1995, Nucleic Acid Research, 23:1087-1088, Friezner-Degen et al, 1986, J.biol.chem.261:6972-698, BD Biosciences Clontech, Palo Alto, Calif.) can be used to isolate infectious sequences. Genome walking techniques are particularly suitable for identifying and isolating sequences adjacent to the novel sequences identified by the methods of the present invention. Based on the novel AAV capsid sequences and rep sequences provided herein, this technique can also be used to isolate Inverted Terminal Repeats (ITRs) of the novel AAV.

Novel AAV amino acid sequences, peptides and proteins can be expressed from the AAV nucleic acid sequences of the invention. In addition, these amino acid sequences, peptides and proteins can also be produced by other methods known in the art, including, for example, chemical synthesis, other synthetic methods, or other methods. Any of the AAV capsid sequences provided herein can be readily produced using a variety of methods.

Suitable production techniques are well known to those skilled in the art. See, for example: sambrook et al, molecular cloning: a Laboratory Manual (Molecular Cloning: A Laboratory Manual), Cold spring harbor Press (Cold spring harbor, New York). Alternatively, peptides can be synthesized by well-known Solid Phase Peptide Synthesis methods (Merrifield, J.Am.chem.Soc, 85:2149 (1962); Stewart and Young, Solid Phase Peptide Synthesis (Freeman, san Francisco, 1969), pp.27-62). These and other suitable production methods are known to those skilled in the art and do not constitute a limitation of the present invention.

The sequences, proteins and fragments of the invention may be produced by a variety of suitable methods, including recombinant production, chemical synthesis or other synthetic methods. Such production methods are known to those skilled in the art and do not constitute a limitation of the present invention.

Production of rAAV with novel AAV capsids

The invention includes novel AAV capsid sequences produced by mutation following identification of a single mutation according to the methods of the invention. The invention further includes novel AAV rh.20, rh.32/33, rh.39, rh.46, rh.73, and rh.74 capsid sequences (SEQ ID Nos: 1-6).

In another aspect, the invention provides molecules for the generation of viral vectors that deliver heterologous genes or other nucleic acid sequences to target cells using the novel AAV sequences of the invention (including fragments thereof).

Molecules of the invention containing AAV sequences include various genetic elements (vectors) that can be delivered to a host cell, such as: naked DNA capable of carrying sequences, plasmids, phages, transposons, cosmids, episomes, proteins in non-viral delivery vectors (e.g., lipid-based vehicles), viruses, and the like.

The selected vector may be delivered by a variety of suitable methods, including transfection, electroporation, liposome delivery, membrane fusion techniques, high-speed DNA-coated beads, viral infection, and protoplast fusion. Methods for constructing embodiments of this aspect of the invention are known to those skilled in the art of nucleic acid manipulation, including genetic engineering, recombinant engineering and synthetic techniques. See, for example: sambrook et al, molecular cloning: a Laboratory Manual (Molecular Cloning: A Laboratory Manual), Cold spring harbor Press, Cold spring harbor, New York.

In one embodiment, the vectors of the invention contain, among other elements, sequences encoding the AAV capsids of the invention, or fragments thereof. In another embodiment, the vectors of the invention contain at least a sequence encoding an AAV rep protein or fragment thereof. Optionally, the vectors of the invention may contain AAV cap and rep proteins. In vectors with both AAV rep and cap, the AAV rep and AAV cap sequences may be derived from AAV from the same clade. Alternatively, the invention provides vectors containing rep and cap sequences from different AAV's. In one embodiment, the rep and cap sequences are expressed from sources (e.g., separate vectors, or host cells and vectors) that are independent of each other. In another embodiment, the rep sequences are fused in-frame to cap sequences from a different AAV to form a chimeric AAV vector. Optionally, the vector of the invention is a vector packaged in an AAV capsid of the invention. These vectors, and others described herein, may further comprise a minigene comprising a selected transgene flanked by an AAV5'ITR and an AAV3' ITR.

Thus, in one embodiment, the vectors described herein contain nucleic acid sequences encoding a complete AAV capsid from the same AAV sequence. Alternatively, these vectors contain sequences encoding a synthetic capsid comprising one or more fragments of a singleton-corrected AAV capsid fused to a heterologous AAV or non-AAV capsid protein (or fragment thereof). These artificial capsid proteins are selected from a discontinuous portion of the capsid corrected for singleton mutation or from other AAV capsids. The purpose of these changes is to increase expression, yield and/or improve purification in the selected expression system, or for other purposes (e.g., to change tropism or to modify neutralizing antibody epitopes).

The vectors described herein, e.g., plasmids, can be used for a variety of purposes, but are particularly useful for producing rAAV containing capsids comprising AAV sequences or fragments thereof. These vectors, including raavs, their elements, constructs, and uses are described in detail herein.

In one aspect, the invention provides a method of producing a recombinant adeno-associated virus (AAV) having a novel AAV capsid of the invention. The method involves culturing a host cell containing a nucleic acid sequence encoding a novel AAV capsid protein of the invention, or a fragment thereof, as defined herein; a functional rep gene; a minigene consisting of at least an AAV Inverted Terminal Repeat (ITR) and a transgene; with sufficient helper functions to package the minigene into an AAV capsid protein.

Culturing in a host cell the components necessary for packaging the AAV minigene into an AAV capsid can be provided transiently (in transit) to the host cell. Alternatively, one or more essential components (e.g., minigene, rep sequence, cap sequence, and/or cofactor function) may be provided by a stable host cell that has been engineered to contain one or more essential components by methods known to those skilled in the art. Preferably, such a stable host cell contains the desired components under the control of an inducible promoter. However, the essential elements may also be under the control of a constitutive promoter. In discussions of regulatory elements suitable for use with transgenes, examples of suitable inducible and constitutive promoters are provided herein. Alternatively, the selected stable host cell may contain the selected element under the control of a constitutive promoter and the other selected element under the control of one or more inducible promoters. For example: stable host cells can be made from 293 cells (containing the E1 co-factor under the control of a constitutive promoter), but which contain rep and/or cap proteins under the control of an inducible promoter. Other stable host cells can also be prepared by those skilled in the art.

The minigenes, rep sequences, cap sequences and cofactors required for the production of the rAAV of the invention may be delivered to the packaging host cell in the form of various genetic elements capable of conveying the sequences carried. The selected genetic element may be delivered by any suitable method, including the methods described herein. Methods for constructing embodiments of this aspect of the invention are known to those skilled in the art of nucleic acid manipulation, including genetic engineering, recombinant engineering and synthetic techniques. See, e.g., Sambrook et al, molecular cloning: a Laboratory Manual (Molecular Cloning: A Laboratory Manual), Cold spring harbor Press, Cold spring harbor, New York. Similarly, methods of producing AAV virions are well known, and selection of appropriate methods does not limit the invention. See, for example: k.fisher et al, j.virol., 70: 520, 532(1993) and U.S. Pat. No. 5,478,745.

Unless otherwise specified, the AAV ITRs described herein and other selected AAV components can be readily selected from any AAV, including but not limited to: AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV9, and other novel AAV sequences of the invention. These ITRs or other AAV components can be readily isolated from AAV sequences using techniques known to those skilled in the art. The AAV may be isolated or obtained from an academic, commercial, or public source (e.g., American Type Culture Collection (ATCC), Manassas, Va.). Alternatively, the AAV sequences can be referenced, for example, to a literature or database (e.g.,

etc.) by synthesis or other suitable methods.

A. Small gene

A minigene consists of at least the transgene and its regulatory sequences and 5 'and 3' Inverted Terminal Repeats (ITRs). In a desirable embodiment, the ITRs of AAV serotype 2 are used. However, other suitable sources of ITRs may be selected. It is this minigene that will be packaged into capsid protein and delivered to the selected host cell.

1. Transgenosis

A transgene is a nucleic acid sequence that encodes a polypeptide, protein, or other product of interest and is heterologous to its flanking vector sequences. The nucleic acid coding sequence is operably linked to regulatory components in a manner that allows for transcription, translation, and/or expression of the transgene in a host cell.

The composition of the transgene sequence depends on the use of the resulting vector. For example: one class of transgenic sequences comprises a reporter sequence that, upon expression, produces a detectable signal. Such reporter sequences include, but are not limited to, DNA sequences encoding: beta-lactamase, beta-galactosidase (LacZ), alkaline phosphatase, thymokinase, Green Fluorescent Protein (GFP), Enhanced GFP (EGFP), Chloramphenicol Acetyltransferase (CAT), luciferase, membrane-bound proteins (e.g., CD2, CD4, CD8), influenza hemagglutinin protein, and other substances known in the art for which high affinity antibodies exist or can be produced by conventional methods, and fusion proteins containing a membrane-bound protein suitably fused to an antigen-labeled region of hemagglutinin or Myc, among other substances.

When these coding sequences are associated with regulatory elements that drive their expression, signals can be provided that are detected by conventional methods, including enzymatic, radiographic, colorimetric, fluorescent or other spectroscopic assays, fluorescence activated cell sorting assays, and immunoassays, including enzyme linked immunosorbent assays (ELISAs), Radioimmunoassays (RIA), and immunohistochemistry. For example: when the marker sequence is the LacZ gene, the presence of the signal-carrying vector is detected by measuring the activity of beta-galactosidase. When the transgene is green fluorescent protein or luciferase, the vector carrying the signal can be observed photometrically by the generation of color or light.

Desirably, however, the transgene is a non-marker sequence encoding a product of biological or medical use, such as a protein, peptide, RNA, enzyme, dominant negative mutant, or catalytic RNA. Desirable RNA molecules include tRNA, dsRNA, ribosomal RNA, catalytic RNA, siRNA, small hairpin RNA, trans-splicing RNA, and antisense RNA. An example of a useful RNA sequence is one that inhibits or eliminates expression of a target nucleic acid sequence in a treated animal. In general, suitable target sequences include tumor targets and viral diseases. Such as tumor targets and viruses as described in the immunogenic section below.

Transgenes may be used to correct or reduce gene defects, including defects in which normal genes are expressed at levels below normal or in which functional gene products are not expressed. Alternatively, the transgene may provide a cell with a product that is not otherwise expressed in that cell type or in that host. Preferred types of transgene sequences encode therapeutic proteins or polypeptides that are expressed in the host cell. The invention further includes the use of multiple transgenes. In some cases, different transgenes may be used to encode individual subunits of a protein, or to encode different peptides or proteins. This is particularly suitable when the DNA encoding the protein subunit is large, such as an immunoglobulin, platelet-derived growth factor or dystrophin. To allow the cells to produce multi-subunit proteins, the cells are infected with recombinant viruses, each containing a different subunit. Alternatively, different subunits of a protein may be encoded by the same transgene. In this case, a single transgene comprises DNA encoding all subunits, with the DNA of each subunit separated by an Internal Ribosome Entry Site (IRES). This is particularly suitable when the DNA encoding each subunit is small, for example the total volume of DNA encoding the subunit and IRES is less than 5 kilobase pairs (5 kb). As an alternative to IRES, the DNA may be separated by a sequence encoding a 2A peptide which is self-cleaving at a post-translational stage. See, for example: m.l.donnelly et al, j.gen.virol., 78 (first part): 13-21(1 month 1997); furler, s. et al, Gene ther, 8 (11): 864-873 (month 6 2001); klump h. et al, Gene ther., 8 (10): 811-817 (5 months 2001). The 2A peptide is significantly smaller than IRES, making it well suited for use when space is a limiting factor. More commonly, where the transgene is large, composed of multiple subunits, or two transgenes are co-delivered, rAAV carrying the desired transgene or subunit are allowed to be shared such that they are concatenated to form a single vector genome in vivo. In such embodiments, the first AAV may carry an expression cassette for expression of one transgene and the second AAV may carry an expression cassette for a different transgene for co-expression in a host cell. However, the selected transgene may encode any biologically active or other product, such as: the desired product was investigated.

One skilled in the art can readily select the appropriate transgene. The choice of transgene does not limit the invention.

2. Adjusting element

In addition to the above major elements for minigenes, the vectors also contain conventional control elements operatively linked to the transgene in a manner that allows transcription, translation and/or expression of the transgene in the cells transfected with the plasmid vectors produced by the invention or infected with a virus. Sequences "operably linked" herein include expression control sequences that are contiguous with the gene of interest and control sequences that function in trans (in trans) or that are some distance away to control the expression of the gene of interest.

Expression control sequences include suitable transcription initiator, terminator, promoter and enhancer sequences; efficient RNA processing signals, such as splicing and polyadenylation (polyA) signals; sequences that stabilize cytoplasmic mRNA; sequences that enhance translation efficiency (i.e., Kozak consensus sequence); sequences that enhance protein stability; and sequences that enhance secretion of the encoded product when desired. Many expression control sequences, including natural, constitutive, inducible, and/or tissue-specific promoters, are known and available in the art.

Examples of constitutive promoters include, but are not limited to: the retroviral Rous Sarcoma Virus (RSV) LTR promoter (optionally linked to the RSV enhancer), the Cytomegalovirus (CMV) promoter (optionally linked to the CMV enhancer) [ see, for example: boshirt et al, Cell, 41: 521-530(1985), SV40 promoter, dihydrofolate reductase promoter, β -actin promoter, phosphoglycerate kinase (PGK) promoter, and EFl promoter (Invitrogen). Inducible promoters are capable of regulating gene expression and may be regulated by exogenously supplied compounds, environmental factors (e.g., temperature), or specific physiological states, such as acute phase, specific differentiation state of the cell, or acting only in replicating cells. Inducible promoters and inducible systems are available from a variety of commercial sources, including but not limited to Invitrogen, Clontech, and Ariad. Many other systems are known and can be readily selected by those skilled in the art. Examples of inducible promoters regulated by exogenous compounds include the zinc-induced Metallothionein (MT) promoter, dexamethasone (Dex) -induced Mouse Mammary Tumor Virus (MMTV) promoter, T7 polymerase promoter system [ international patent publication No. WO 98/10088], ecdysone insect promoter [ No et al, proc.natl.acad.sci. us, 93: 3346-3351(1996) ], the tetracycline repression system [ Gossen et al, Proc. Natl. Acad. Sci. USA, 89: 5547-5551(1992) ], the tetracycline induction system [ Gossen et al, Science, 268: 1766-1769(1996), see also Harvey et al, curr, opin, chem, biol., 2: 512-: 239, 243(1997) and Wang et al, Gene ther, 4: 432-: 2856-2872(1997)]. Other inducible promoter types useful in the present invention are those that are regulated by a particular physiological state, such as temperature, acute phase, particular differentiation state of the cell, or act only in replicating cells.

In another embodiment, a native promoter for the transgene is used. Where expression of the transgene is desired to mimic native expression, a native promoter may be preferred. When expression of a transgene must be regulated in a transient or developmental manner, or regulated in a tissue-specific manner or in response to a particular transcriptional stimulus, a native promoter may be used. In additional embodiments, other natural expression control elements, such as enhancer elements, polyadenylation sites, or Kozak consensus sequences may also be used to mimic natural expression.

Another embodiment of the transgene comprises a gene operably linked to a tissue specific promoter. For example, if expression in skeletal muscle is desired, a promoter active in muscle should be used. This includes promoters of genes encoding the following products: skeletal beta-actin, myosin light chain 2A, dystrophin, muscle creatine kinase, and synthetic muscle promoters with higher activity than the natural promoters (see: Li et al, nat. Biotech., 17: 241) -245 (1999)). Examples of known tissue-specific promoters are liver-specific (albumin, Miyatake et al, J.Virol., 71: 5124-32 (1997); hepatitis B virus core promoter, Sandig et al, Gene ther., 3: 1002-9 (1996): alpha-fetoprotein (AFP), Arbuthrot et al, hum.Genether., 7: 1503-14(1996)), osteocalcin of bone (Stein et al, mol.biol.Rep., 24: 185-96 (1997)); bone sialoprotein (Chen et al, J.bone Miner. Res., 11: 654-64(1996)), lymphocyte-specific (CD2, Hansal et al, J.Immunol.161: 1063-8 (1998); immunoglobulin heavy chain; T cell receptor chain), Neuron-specific (e.g., Neuron-specific enolase (NSE) promoter (Andersen et al, cell. mol. Neurobiol., 13: 503-15(1993)), neurofilament light chain gene (Piccioli et al, Proc. Natl. Acad. Sci., USA, 88: 5611-5(1991)), and Neuron-specific vgf gene (Piccioli et al, Neuron, 15: 373-84(1995)), etc.).

Optionally, the plasmid carrying the transgene for therapeutic use may also contain a selectable marker gene or reporter gene, e.g., a sequence encoding geneticin resistance, hygromycin resistance, puromycin (puromycin) resistance, or the like. Such a selectable reporter gene or marker gene (preferably located outside the viral genome to be rescued by the method of the invention), e.g., ampicillin resistance, can be used to indicate the presence of the plasmid in the bacterial cell. Other components of the plasmid may include an origin of replication. These and other promoter and vector elements can be selected by conventional methods, and many such sequences are available [ see, e.g.: sambrook et al, and references cited herein ].

For ease of reference, the combination of transgene, promoter/enhancer and 5 'and 3' AAV ITRs is referred to herein as a "minigene". Such minigenes can be designed by conventional techniques in view of the teachings of the present invention.

3. Delivery of minigenes to packaging host cells

Any suitable vector, such as a plasmid, for delivery to a host cell may be used to carry the minigene. The plasmids used in the present invention may be engineered into plasmids suitable for replication and integration (optional) in prokaryotic cells, mammalian cells, or both. These plasmids (or other vectors carrying 5'AAV ITR-heterologous molecule-3' AAV ITR) contain sequences that allow minigenes to replicate in eukaryotic and/or prokaryotic cells and selectable markers for use in these systems. The selectable marker gene or reporter gene may include sequences encoding geneticin resistance, hygromycin resistance, puromycin resistance, or the like. These plasmids may also contain certain selectable reporter or marker genes, such as ampicillin resistance, which may be used to indicate the presence of the vector in the bacterial cell. Other components of the plasmid may include an origin of replication and an amplicon, such as an amplicon system using Epstein Barr virus nuclear antigen. The amplicon system or other similar amplicon component allows high copy episomal replication in cells. The molecule carrying the minigene is preferably transfected into a cell in which it can transiently exist. Alternatively, the minigene (carrying the 5'AAV ITR-heterologous molecule-3' AAV ITR) may be stably integrated into the genome of the host cell, either into the chromosome or as an episome. In certain embodiments, the minigene may optionally exist in multiple copies in the form of head-to-head, head-to-tail, or tail-to-tail concatemers. Suitable transfection techniques are known and can be readily used to deliver minigenes to host cells.

Typically, when a vector containing a minigene is delivered by transfection, about 5. mu.g to 100. mu.g DNA, about 10. mu.g to 50. mu.g DNA will typically be delivered at about 1X10⁴-1×10¹³Individual cell or about 1X10⁵And (4) cells. However, one skilled in the art can adjust the ratio of vector DNA amount to host cell, taking into account factors such as the vector chosen, the method of delivery, and the host cell chosen.

Rep and Cap sequences

In addition to the minigene, the host cell contains sequences that drive expression of the novel AAV capsid proteins of the invention (or capsid proteins containing fragments thereof) in the host cell and rep sequences from the same source as the AAV ITRs in the minigene or from a cross-complementary source. The AAV cap and rep sequences may be obtained from the AAV sources described above independently of each other and may be introduced into the host cell in any manner known to those of skill in the art as described above. In addition, sequences encoding various major rep proteins may be provided from different AAV sources (e.g., AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9) in the pseudopackaging of AAV vectors. For example: the rep78/68 sequence is derived from AAV2, while the rep52/40 sequence is derived from AAV 8.

In one embodiment, the host cell stably contains the capsid protein under the control of a suitable promoter (e.g., as described above). In this embodiment, the capsid protein is preferably expressed under the control of an inducible promoter. In another embodiment, the capsid protein is provided to the host cell in a transfor mode (in trans). When delivered to a host cell in a transfectional manner, the capsid protein can be delivered by a plasmid containing sequences required to direct expression of the selected capsid protein in the host cell. When delivered to a host cell in a transfectional manner, the plasmid carrying the capsid protein preferably also carries other sequences required for packaging the rAAV, such as rep sequences.

In another embodiment, the host cell stably contains a rep sequence under the control of a suitable promoter (as described above). In this embodiment, the major rep protein is preferably expressed under the control of an inducible promoter. In another embodiment, the rep protein is provided to the host cell in a transfer mode (in trans). When delivered to a host cell in a transfor manner, the rep protein may be delivered by a plasmid containing the sequences required to direct expression of the selected rep protein in the host cell. When delivered to a host cell in a transfectional manner, the plasmid carrying the capsid protein also preferably carries other sequences required for packaging the rAAV, such as rep and cap sequences.

Thus, in one embodiment, the rep and cap sequences may be located on a single nucleic acid molecule transfected into a host cell and stably present in the cell as episomes. In another embodiment, the rep and cap sequences are stably integrated into the chromosome of the cell. In another embodiment, the rep and cap sequences are transiently expressed in the host cell. For example, useful nucleic acid molecules for such transfection contain, from 5 'to 3', a promoter, an optional spacer inserted between the promoter and the start site of the rep gene sequence, an AAV rep gene sequence, and an AAV cap gene sequence.

Optionally, rep and/or cap sequences may be provided on a vector containing additional DNA sequences to be introduced into the host cell. For example: the vector may contain a rAAV construct comprising a minigene. The vector may contain one or more genes encoding helper factor functions such as adenovirus proteins E1, E2a, and E4 ORF6, and genes for VAI RNA.

The promoter used in this construct is preferably a constitutive, inducible or native promoter of a character known to the person skilled in the art or as described hereinbefore. In one embodiment, the AAV P5 promoter sequence is used. The selection of AAV to provide these sequences is not a limitation of the present invention.

In another preferred embodiment, the promoter for rep is an inducible promoter, such as those described above for the transgenic regulatory elements. One of the preferred promoters for Rep expression is the T7 promoter. Cells constitutively or inducibly expressing T7 polymerase are transfected or transformed with a vector comprising a rep gene and a cap gene regulated by the T7 promoter. See International patent publication No. W098/10088, published on 12/3/1998.

In designing the carrier, spacers are optional elements. The spacer is a DNA sequence inserted between the promoter and the ATG start site of the rep gene. The spacers may have any desired design; that is, it may be a random nucleotide sequence, or may encode a gene product, such as a marker gene. The spacer may contain genes that typically include initiation/termination and polyA sites. The spacer may be a non-coding DNA sequence, a repetitive non-coding sequence, a coding sequence without transcriptional control, or a coding sequence with transcriptional control from a prokaryote or eukaryote. Two typical sources of spacer sequences are bacteriophage ladder sequences or yeast ladder sequences, both of which are available from, for example, Gibco or Invitrogen, among others. The spacer may be of any size sufficient to reduce the expression of the rep78 and rep68 gene products such that the expression of the rep52, rep40, and cap gene products is at normal levels. Thus, the spacer has a length ranging from about l 0bp to about 10.0kbp, preferably from about 100bp to about 8.0 kbp. To reduce the likelihood of recombination, the spacer length is preferably less than 2 kbp; however, the present invention is not limited thereto.

While the molecule providing rep and cap may be transiently (i.e., by transfection) present in the host cell, it is preferred that one or both of the rep and cap proteins be stably expressed in the host cell with a promoter controlling its expression, e.g., as an episome or by integration into the host cell chromosome. The methods used to construct embodiments of this aspect of the invention are conventional genetic engineering or recombinant engineering techniques, such as those described in the foregoing references. Although the present specification provides illustrative examples of specific constructs, one skilled in the art can use the information provided herein to select spacers, P5 promoter and other elements (including at least one translation initiation and termination signal), and optionally additional polyadenylation sites, to select and design other suitable constructs.

In another embodiment of the invention, the rep or cap protein may be stably provided by the host cell.

C. Cofactor function

For packaging the rAAV of the invention, the packaging host cell also requires cofactor function. Optionally, these functions may be provided by the herpes virus. The required ancillary functions are preferably provided by human or non-human primate adenovirus sources, respectively, such as those described above and/or obtained from a variety of sources (including American Type Culture Collection (ATCC), Manassas, Va.). In a presently preferred embodiment, the host cell is provided with and/or contains an E1a gene product, an E1b gene product, an E2a gene product, and/or an E4 ORF6 gene product. The host cell may contain other adenoviral genes, such as VAI RNA, but these genes are not required. In a preferred embodiment, no other adenoviral genes or gene functions are present in the host cell.

"adenoviral DNA expressing the E1a gene product" refers to various adenoviral sequences encoding E1a or functional portions thereof. Adenoviral DNA expressing the E2a gene product and adenoviral DNA expressing the E40 RF6 gene product are defined similarly. Also included are alleles or other modifications of the adenoviral gene or functional portion thereof. Such modifications include both those specifically introduced by conventional genetic engineering or mutagenesis techniques to enhance adenoviral function in some manner, and naturally occurring allelic variants. Such modifications and methods for obtaining adenoviral gene function by DNA manipulation are known to those skilled in the art.

Adenovirus E1a, E1b, E2a, and/or E4 ORF6 gene products, as well as various other desired helper factor functions, can be provided using a variety of methods for their expression in a cell. Each sequence encoding these products may be located on a separate vector, or one or more genes may be located on the same vector. The vector may be any of the various vectors known in the art or described supra, including plasmids, cosmids, and viruses. The vector may be introduced into the host cell by a variety of methods known in the art or previously described, including transfection, infection, electroporation, liposome delivery, membrane fusion techniques, high-speed DNA-coated beads, viral infection and protoplast fusion, and the like. One or more adenoviral genes can be stably integrated into the host cell genome, stably expressed as episomes, or transiently expressed. The gene product may be expressed in its entirety transiently, either in episomes or stably integrated; alternatively, some gene products may be stably expressed while others are transiently expressed. Furthermore, the promoter of each adenoviral gene can be selected independently of each other from a constitutive promoter, an inducible promoter or a native adenoviral promoter. Promoters may be regulated by a particular physiological state of an organism or cell (i.e., differentiation state or replicating or resting cells) or by other means such as exogenously added factors.

D. Host cells and packaging cell lines

The host cell itself may be selected from a variety of organisms, including prokaryotic (e.g., bacterial) cells and eukaryotic cells, including insect cells, yeast cells, and mammalian cells. Particularly desirable host cells are selected from a characteristic mammalian species, including, without limitation, the following: a549, WEHI, 3T3, 10T1/2, BHK, MDCK, COS1, COS7, BSCl, BSC40, BMT10, VERO, W138, HeLa, 293 cells (expressing functional adenovirus E1), Saos, C2C12, L cells, HT1080, HepG2 and primary fibroblasts, hepatocytes and myoblasts derived from mammals including humans, monkeys, mice, rats, rabbits and hamsters. The mammalian source of the selected cells and the type of mammalian cells (i.e., fibroblasts, hepatocytes, tumor cells, etc.) do not limit the invention. The requirements for the cells used are: it does not carry any adenoviral genes other than E1, E2a and/or E40 RF 6; it does not contain any other viral genes that could cause homologous recombination of contaminating viruses during rAAV production; and, it can be infected or transfected with DNA and express the transfected DNA. In a preferred embodiment, the host cell is a cell comprising stably transfected rep and cap.

One of the host cells used in the present invention is a host cell stably transformed with rep and cap encoding sequences and transfected with adenovirus E1, E2a and E40 RF6 DNA and constructs carrying minigenes as described previously. Stable rep and/or cap expressing cell lines, such as B-50 (International patent application publication No. W099/15685), or the cell lines described in U.S. Pat. No. 5,658,785, may also be used similarly. Another desirable host cell contains the essential adenoviral DNA required for expression of E4 ORF 6. Other cell lines can also be constructed using the novel singleton-corrected AAV cap sequences of the present invention.

The invention of the preparation of host cells involved such as assembly of selected DNA sequences and technology. Such assembly may be accomplished using conventional techniques. Such techniques include cDNA and genomic cloning, using overlapping oligonucleotide sequences of adenovirus and AAV genomes, in conjunction with polymerase chain reaction, synthetic methods, and other suitable methods of providing the desired nucleotide sequences, which are well known and described in Sambrook et al, cited above.

These molecules (e.g., plasmids or viruses) can also be introduced into the host cell using techniques known to the skilled artisan and discussed herein. In a preferred embodiment, standard transfection techniques are used, such as: cap0₄Transfection or electroporation, and/or infection of cell lines, such as the human embryonic kidney cell line HEK293 (a human kidney cell line containing a functional adenovirus E1 gene that provides the E1 protein in trans), with a hybrid adenovirus/AAV vector.

It will be readily appreciated by those skilled in the art that the novel AAV sequences of the present invention can be readily adapted for use in the above and other expression vector systems for gene delivery in vitro, ex vivo or in vivo. Similarly, one skilled in the art can readily select other AAV genomic fragments of the invention for use in various rAAV and non-rAAV vector systems. These vector systems include, for example: lentivirus, retrovirus, poxvirus, vaccinia virus, and adenovirus systems, among others. The choice of these vector systems does not limit the invention.

Thus, the present invention further provides vectors generated using the nucleic acid and amino acid sequences of the novel AAV of the present invention. Such vectors can be used for a variety of purposes, including the delivery of therapeutic molecules and in vaccine administration protocols (vaccine domains). Recombinant AAV comprising the novel AAV capsids of the invention are particularly desirable for delivery of therapeutic molecules. These and other vector constructs containing the novel AAV sequences of the invention may be used in vaccine administration regimens, for example: for co-delivery of cytokines, or for delivery of the immunogen itself.

Recombinant viruses and uses thereof

One skilled in the art can use the techniques described herein to generate rAAV having a capsid of an AAV of the invention or a capsid thereof containing one or more fragments of an AAV of the invention. In one embodiment, full-length capsids from singleton-corrected AAV are used.

A. Delivery of viruses

In another aspect, the invention provides a method of delivering a transgene to a host involving transfecting or infecting a selected host cell with a recombinant viral vector produced from a singleton-corrected AAV (or functional fragment thereof) of the invention. Methods for delivery are well known to those skilled in the art and do not limit the present invention.

In a desirable embodiment, the invention provides a method for AAV-mediated delivery of a transgene to a host. The method involves transfecting or infecting a selected host cell with a recombinant viral vector containing a transgene of choice under the control of sequences directing its expression and a modified capsid protein.

Optionally, a sample from the host may first be assayed for the presence of antibodies to the selected AAV source (e.g., a serotype). Various assay formats for detecting neutralizing antibodies are well known to those skilled in the art. The choice of such an assay does not limit the invention. See, for example: fisher et al, Nature med, 3 (3): 306-312 (3 months 1997) and w.c. manning et al, Human Gene Therapy, 9: 477-485 (1/3/1998). The results of this assay, e.g., no specific neutralizing antibodies of a particular capsid origin, can be used to determine which AAV vector containing a capsid protein of a particular origin is preferred for delivery.

In one aspect of this method, a vector having a different AAV capsid protein can be delivered before or after delivery of a vector having an AAV capsid protein of the invention. Thus, gene delivery by rAAV vectors can be used to repeatedly deliver genes into selected host cells. Ideally, the later-administered rAAV vector carries the same transgene as in the first rAAV vector, but the later-administered vector contains capsid proteins that are derived from a different source (and preferably a different serotype) than the first vector. For example: if the first vector has a capsid protein corrected by a singleton mutation, the subsequently administered vector may have a capsid protein selected from other AAV, e.g., an AAV which may be of another serotype or of another clade.

Optionally, multiple rAAV vectors can be concatenated into a single vector genome in vivo by co-administering multiple rAAV vectors for delivery of a large transgene or multiple transgenes. In such embodiments, a first AAV may carry an expression cassette for expression of a single transgene (or subunit thereof), and a second AAV may carry an expression cassette for expression of a second transgene (or a different subunit) for co-expression in a host cell. The first AAV can carry an expression cassette for a first portion of a polycistronic construct (e.g., a promoter and a transgene, or a subunit) and the second AAV can carry an expression cassette for a second portion of the polycistronic construct (e.g., a transgene or subunit and a polyA sequence). These two portions of the polycistronic construct are concatamerized in vivo into a single vector genome that co-expresses the transgenes delivered by the first and second AAV. In such embodiments, the rAAV vector carrying the first expression cassette and the rAAV vector carrying the second expression cassette may be contained in a single pharmaceutical composition for delivery. In other embodiments, two or more rAAV vectors are delivered in separate pharmaceutical compositions, which may be administered substantially simultaneously or slightly sequentially.

The above recombinant vectors can be delivered into host cells according to the disclosed methods. rAAV, preferably suspended in a physiologically compatible carrier, can be administered to a human or non-human mammalian patient. One skilled in the art can readily select an appropriate vector depending on the indication for which viral delivery is intended. For example, suitable carriers include saline that can be formulated with various buffers (e.g., phosphate buffered saline). Other examples of carriers include sterile saline, lactose, sucrose, calcium phosphate, gelatin, glucose, agar, pectin, peanut oil, sesame oil and water. The choice of the carrier does not limit the invention.

Optionally, the compositions of the invention may contain, in addition to the rAAV and the vector, other conventional pharmaceutical components, such as preservatives or chemical stabilizers. Suitable preservatives are, for example, chlorobutanol, potassium sorbate, sorbic acid, sulfur dioxide, propyl gallate, parabens, ethyl vanillin, glycerol, phenol and p-chlorophenol. Suitable chemical stabilizers include gelatin and albumin.

The vector should be administered in an amount sufficient to transfect the cells and provide sufficient gene delivery and expression levels to provide therapeutic efficacy without adverse side effects, or medically acceptable physiological effects, as will be determined by one of skill in the medical arts. Conventional and pharmaceutically acceptable routes of administration include, but are not limited to: direct delivery to the target organ (e.g., liver (optionally via hepatic artery) or lung), oral, inhalation, intranasal, intratracheal, intraarterial, intraocular, intravenous, intramuscular, subcutaneous, intradermal, and other parenteral routes of administration. If desired, various routes of administration may be combined.

The dosage of the viral vector depends mainly on factors such as the condition to be treated, the age, weight and health of the patient and thus may vary from patient to patient. For example, a human therapeutically effective dose of a viral vector will generally comprise a concentration of about 1X10⁹-1×10¹⁶0.1mL to 100mL of a solution of each genomic viral vector. The preferred human dose for delivery to the large organs (e.g., liver, muscle, heart and lung) may be about 5X 10¹⁰-5×10¹³AAV genomes/kg, approximately 1-100mL in volume. The preferred dose for delivery to the eye is about 5X 10⁹-5×10¹²Copies of the genome, in a volume of about 0.1mL to 1 mL. The dosage can be adjusted to balance side effects with therapeutic efficacy, and such dosage can vary depending on the particular therapeutic use of the recombinant vector. The expression level of the transgene can be monitored to determine the frequency of administration to obtain a viral vector, preferably an AAV vector containing a minigene. Optionally, the compositions of the invention may be used for immunization according to a dosing regimen similar to that described for therapeutic purposes.

Examples of therapeutic and immunogenic products for delivery using the AAV-containing vectors of the invention are provided below. These vectors may be used in various therapeutic or vaccination protocols described herein. In addition, these carriers can be used in combination with one or more other carriers or active ingredients for delivery as required by the therapeutic and/or vaccination regimen.

B. Therapeutic transgenes

Useful therapeutic products encoded by transgenes include hormones and growth and differentiation factors, including but not limited to: insulin, glucagon, Growth Hormone (GH), parathyroid hormone (PTH), growth hormone releasing factor (GRF), Follicle Stimulating Hormone (FSH), Luteinizing Hormone (LH), human chorionic gonadotropin (hCG), Vascular Endothelial Growth Factor (VEGF), angiopoietin, angiostatin, Granulocyte Colony Stimulating Factor (GCSF), Erythropoietin (EPO), Connective Tissue Growth Factor (CTGF), basic fibroblast growth factor (bFGF), acidic fibroblast growth factor (aFGF), Epidermal Growth Factor (EGF), platelet-derived growth factor (PDGF), insulin growth factors I and II (IGF-I and IGF-II), any of the transforming growth factor alpha superfamily (including any of TGF alpha, activin, inhibin), or Bone Morphogenetic Protein (BMP) BMP1-15, heregulin/neuregulin/ARIA/Neu Differentiation Factor (NDF) family of growth factors, Nerve Growth Factor (NGF), Brain Derived Neurotrophic Factor (BDNF), neurotrophins NT-3 and NT-4/5, ciliary neurotrophic factor (CNTF), glial cell line derived neurotrophic factor (GDNF), neurturin, collectin, any of the semaphorin/Wardysin families, netrin-1 and netrin-2, Hepatocyte Growth Factor (HGF), ephrin, noggin, sonic hedgehog protein and tyrosine hydroxylase.

Other useful transgene products include proteins that modulate the immune system, including but not limited to: cytokines and lymphokines, such as Thrombopoietin (TPO), Interleukins (IL) IL-1 through IL-25 (including, for example, IL-2, IL-4, IL-12, and IL-18), monocyte chemistry inducing protein, leukemia inhibitory factor, granulocyte-macrophage colony stimulating factor, Fas ligand, tumor necrosis factors alpha and beta, interferons alpha, beta, and gamma, stem cell factor, flk-2/flt3 ligand. Gene products produced by the immune system may also be used in the present invention. These products include, but are not limited to: immunoglobulin IgG, IgM, IgA, IgD and IgE, chimeric immunoglobulins, humanized antibodies, single chain antibodies, T cell receptors, chimeric T cell receptors, single chain T cell receptors, class I and class ii MHC molecules, and engineered immunoglobulin and MHC molecules. Useful gene products also include complement regulatory proteins such as complement regulatory protein, Membrane Cofactor Protein (MCP), Decay Accelerating Factor (DAF), CR1, CF2, and CD 59.

Other useful gene products include any of hormone receptors, growth factors, cytokines, lymphokines, regulatory proteins, and immune system proteins. The present invention encompasses cholesterol-and/or lipid-modulated receptors, including Low Density Lipoprotein (LDL) receptors, High Density Lipoprotein (HDL) receptors, Very Low Density Lipoprotein (VLDL) receptors, and clearance receptors. The present invention also includes the following gene products: for example, members of the steroid hormone receptor superfamily, including glucocorticoid receptors and estrogen receptors, vitamin D receptors, and other nuclear receptors. In addition, useful gene products include transcription factors such as jun, fos, max, mad, serum effector (SRF), AP-1, AP2, myb, MyoD and myogenin, protein-containing ETS-boxes, TFE3, E2F, ATFl, ATF2, ATF3, ATF4, ZF5, NFAT, CREB, HNF-4, C/EBP, SP1, CCAAT-box binding proteins, interferon regulatory factor (IRF-1), Wilms tumor protein, ETS-binding proteins, STAT, GATA-box binding proteins such as the forkhead protein family of GATA-3 and winged helix proteins.

Other useful gene products include carbamoyl synthetase I, ornithine transcarbamylase, argininosuccinate synthetase, argininosuccinate lyase, arginase, fumarylacetoacetate hydrolase, phenylalanine hydroxylase, alpha-1 antitrypsin, glucose-6-phosphatase, porphobilinogen deaminase, cystathionine beta-synthase, branched chain keto acid decarboxylase, albumin, isovaleryl-CoA dehydrogenase, propionyl-CoA carboxylase, methylmalonyl-CoA mutase, glutaryl-CoA dehydrogenase, insulin, beta-glucosidase, pyruvate carboxylate, liver phosphorylase, phosphorylase kinase, glycine decarboxylase, H-protein, T-protein, cystic fibrosis transmembrane conductance regulator (CFTR) sequence and dystrophin gene products [ for example: small-or micro-dystrophin ]. Other useful gene products include enzymes that can be used for various conditions caused by a lack of enzyme activity, such as enzyme replacement therapy. For example, enzymes containing mannose-6-phosphate may be used to treat lysozyme storage disease (e.g., the gene encoding β -Glucuronidase (GUSB)).

Other useful gene products include products for treating hemophilia, including hemophilia B (including factor IX) and hemophilia A (including factor VIII and variants thereof, e.g., the light and heavy chains of heterodimers and B-deleted domains; U.S. Pat. No. 6,200,560 and U.S. Pat. No. 6,221,349). The factor VIII gene encodes 2351 amino acids, a protein with six domains, designated sequentially from amino to carboxy as a1-a2-B-A3-C1-C2[ Wood et al, Nature, 312: 330 (1984); vehar et al, Nature, 312: 337 (1984); and Toole et al, Nature, 342: 337(1984)]. Human factor VIII is processed intracellularly to produce a heterodimer consisting essentially of a heavy chain containing a1, a2, and B domains and a light chain containing A3, C1, and C2 domains. The single chain polypeptide and heterodimer circulate in plasma as inactive precursors until activated by thrombin cleavage between the a2 and B domains, thereby releasing the B domain and forming a heavy chain consisting of the a1 and a2 domains. The protein-activated procoagulant form does not contain a B domain. Furthermore, in native proteins, the two polypeptide chains flanking the B domain ("a" and "B") bind divalent calcium cations.

In some embodiments, the minigene contains the first 57 base pairs of the factor VIII heavy chain encoding a 10 amino acid signal sequence and a human growth hormone (hGH) polyadenylation sequence. In another embodiment, the minigene further comprises the A1 and A2 domains, and the N-terminal 5 amino acids of the B domain, and/or the C-terminal 85 amino acids of the B domain, and the A3, C1, and C2 domains. In additional embodiments, the nucleic acids encoding the factor VIII heavy and light chains are separated by 42 nucleic acids encoding the 14 amino acids of the B domain and contained in a single minigene [ U.S. patent No. 6,200,560 ].

A therapeutically effective amount, as used herein, refers to an amount of AAV vector that produces a sufficient amount of factor VIII to reduce the time required for blood clotting in a subject. Typically, the whole clotting time is greater than 60 minutes for severe hemophiliacs with factor VIII levels less than 1% of normal levels, and about 10 minutes for non-hemophiliacs.

The present invention is not limited to any particular factor VIII sequence. Many natural and recombinant forms of factor VIII have been isolated and produced. Examples of natural and recombinant forms of factor VIII are found in the patent and scientific literature, including U.S. patent No. 5,563,045; 5,451,521, respectively; 5,422,260, respectively; 5,004,803, respectively; 4,757,006, respectively; 5,661,008, respectively; 5,789,203, respectively; 5,681,746; 5,595,886, respectively; 5,045,455, respectively; 5,668,108, respectively; 5,633,150, respectively; 5,693,499, respectively; 5,587,310, respectively; 5,171,844, respectively; 5,149,637, respectively; 5,112,950, respectively; 4,886,876, respectively; international patent publication Nos. WO 94/11503, WO 87/07144, WO 92/16557, WO 91/09122, W097/03195, W096/21035 and WO 91/07490; european patent application nos. EP 0672138, EP 0270618, EP 0182448, EP 0162067, EP 0786474, EP 0533862, EP 0506757, EP 0874057, EP 0795021, EP 0670332, EP 0500734; EP 0232112 and EP 0160457; sanberg et al, World Hemophilia association, 20 th international conference (XXth int. congress of the World fed. of Hemophilia), (1992) and Lind et al, eur.j. biochem., 232: 19(1995).

The nucleic acid sequence encoding the factor VIII described above may be obtained using recombinant methods or from vectors known to contain the sequence. In addition, the desired sequence can also be isolated directly from cells and tissues containing the sequence using standard techniques, such as phenol extraction and PCR with cDNA or genomic DNA [ see, e.g.: sambrook et al ]. In addition to cloning, nucleotide sequences may also be produced synthetically. Overlapping oligonucleotides can be prepared by standard methods and assembled from the overlapping oligonucleotides into a complete coding sequence [ see, e.g.: edge, Nature, 292: 757 (1981); nambari et al, Science, 223: 1299(1984) and Jay et al, j.biol.chem., 259: 6311(1984)].

Furthermore, the present invention is not limited to human factor VIII. Indeed, the present invention is intended to include factor VIII from animals other than humans, including, but not limited to, pet animals (e.g., dogs, cats and horses), livestock (e.g., cows, goats and sheep), laboratory animals, marine animals, large felines (large cat), and the like.

AAV vectors can contain nucleic acids encoding a factor VIII fragment that is biologically inactive per se, but which improves or restores blood clotting time when administered to a subject. For example, as previously described, factor VIII proteins contain two polypeptide chains: heavy and light chains separated by a B domain that will be cleaved off during processing. As demonstrated herein, co-transduction of receptor cells with both the heavy and light chains of factor VIII results in the expression of biologically active factor VIII. Since most hemophiliacs contain mutations or deletions in only one strand (e.g., the heavy or light chain), it is possible to give the patient only the defective strand to complement the other strand.

Other useful gene products include non-naturally occurring polypeptides, such as chimeric or hybrid polypeptides having a non-naturally occurring amino acid sequence containing insertions, deletions, or amino acid substitutions. For example, single-chain engineered immunoglobulins may be used in certain immunocompromised patients. Other types of non-naturally occurring gene sequences, including antisense molecules and catalytic nucleic acids, such as ribozymes, can be used to reduce overexpression of the target.

Reducing and/or modulating gene expression is particularly desirable for the treatment of hyperproliferative diseases characterized by cellular hyperproliferation, such as cancer and psoriasis. Target polypeptides include polypeptides that are produced only in hyperproliferative cells or at higher levels in hyperproliferative cells as compared to normal cells. Target antigens include oncogenes encoding polypeptides such as myb, myc, fyn, and translocation genes encoding polypeptides such as bcr/abl, ras, src, P53, neu, trk, and EGRF. In addition to oncogene products as target antigens, target polypeptides for use in anti-cancer therapy and protective treatment regimens include the variable regions of antibodies produced by B cell lymphomas and the variable regions of T cell receptors of T cell lymphomas, which, in certain embodiments, are also used as target antigens for autoimmune diseases. Other tumor-associated polypeptides may also be used as target polypeptides, such as polypeptides at higher levels in tumor cells, including polypeptides recognized by monoclonal antibody 17-lA and folate binding polypeptides.

Other suitable therapeutic polypeptides and proteins include polypeptides and proteins that treat individuals with autoimmune diseases and disorders by conferring a broad spectrum of basic protective immune responses against autoimmune-related targets, including cellular receptors and cells that produce "self" directed antibodies. T cell mediated autoimmune diseases include Rheumatoid Arthritis (RA), Multiple Sclerosis (MS),

Sarcoidosis, Insulin Dependent Diabetes Mellitus (IDDM), autoimmune thyroiditis, reactive arthritis, ankylosing spondylitis, scleroderma, polymyositis, dermatomyositis, psoriasis, vasculitis, wegener's granulomatosis, crohn's disease, and ulcerative colitis. These diseases are all characterized by T Cell Receptors (TCRs) that bind endogenous antigens and initiate the inflammatory cascade associated with autoimmune diseases.

C. Immunogenic transgenes

The AAV vectors of the invention are preferably designed to avoid generating an immune response against the AAV sequences contained in the vectors. However, these vectors are formulated such that the transgene carried by the vector is expressed to induce an immune response to the selected antigen. For example, to facilitate an immune response, expression of the transgene may be controlled by a constitutive promoter, the vector may be combined with an adjuvant as described herein, and/or the vector may be introduced into degenerated tissue.

Examples of suitable immunogenic transgenes may include immunogenic transgenes selected from various virus families. Examples of virus families that require an immune response to protect against include: picornaviridae, which includes rhinovirus genus that causes about 50% of common cold cases; enteroviruses, which include poliovirus, coxsackievirus, echovirus, and human enterovirus (e.g., hepatitis a virus); and the genus aphthovirus, which causes foot-and-mouth disease primarily in non-human animals. Within the picornaviridae, target antigens include VP1, VP2, VP3, VP4, and VPG. Other virus families include astrovirus and caliciviridae. The caliciviridae family includes norwalk group viruses considered to be an important cause of epidemic gastroenteritis. Another family of viruses that might be expected to be useful for targeting antigens to induce an immune response in a human or non-human animal is the togaviridae family, which includes the genera alphavirus, which includes sindbis virus, ross river virus, and venezuelan, eastern and western equine encephalitis virus, and rubella virus, including rubella virus. The flaviviridae family includes dengue, yellow fever, japanese encephalitis, st. Other target antigens may be produced from the hepatitis c or coronavirus family, which includes many non-human viruses such as infectious bronchitis virus (poultry), porcine infectious gastrointestinal virus (pig), porcine thromboencephalomyelitis virus (pig), feline infectious peritonitis virus (cat), feline enteric coronavirus (cat), canine coronavirus (dog) and human respiratory coronavirus which may cause the common cold and/or non-hepatitis a, b or c, which family of viruses may also be the cause of Severe Acute Respiratory Syndrome (SARS). Within the family coronaviridae, target antigens include E1 (also known as M or matrix protein), E2 (also known as S or spike protein), E3 (also known as HE or hemagglutinin-etibose), glycoproteins (not all coronaviruses) or N (nucleocapsid). He antigen can also be against the arterivirus and rhabdovirus families. Rhabdoviridae include the genera vesiculovirus (e.g., herpes stomatitis virus) and rabies virus (e.g., rabies). Within the Rhabdoviridae, suitable antigens may be derived from either the G protein or the N protein. Filoviridae, including hemorrhagic fever viruses such as marburg and ebola may be suitable sources of antigens. The paramyxoviridae family includes parainfluenza virus type 1, parainfluenza virus type 3, bovine parainfluenza virus type 3, mumps virus (mumps virus), parainfluenza virus type 2, parainfluenza virus type 4, newcastle disease virus (chicken), rinderpest virus, measles virus (which includes measles and canine distemper), and pneumovirus (which includes respiratory syncytial virus). Influenza viruses are classified in the family orthomyxoviridae and are suitable sources of antigens (e.g., HA protein, N1 protein). The bunyaviridae family includes the genera bunyavirus (California encephalitis, Laxos encephalitis), phlebovirus (rift Valley fever), Hantavirus (Primala is a hemahagin fever virus), Neuropyvirus (Neuropygian sheep disease) and various unnamed bungarus viruses (bungavir). The arenaviridae family provides a source of antigens against LCM and lassa fever virus. Another source of antigens is the bornaviridae family. Reoviridae include the genera reovirus, rotavirus (which causes acute gastroenteritis in children), orbivirus and colorado tick fever (colorado tick fever, Lebombo virus (human), equine encephalopathy, bluetongue virus). The retroviral family includes the oncogenic RNA virus subfamily, which includes human and veterinary diseases such as feline leukemia virus, HTLVI and HTLVII, the lentivirus subfamily (including HIV, simian immunodeficiency virus, feline immunodeficiency virus, canine infectious anemia virus, and foamy virus subfamily).

In the case of HIV and SIV, a number of suitable antigens have been described and can be readily selected. Examples of suitable HIV and SIV antigens include, but are not limited to, gag, pol, Vif, Vpx, VPR, Env, Tat, and Rev proteins, and various fragments thereof. For example, fragments of suitable envelope (env) proteins include, for example: gp41, gp140, and gp 120. In addition, various modifications to these and other HIV and SIV antigens have been described. Suitable antigens for this purpose are known to those skilled in the art. For example, sequences encoding gag, pol, Vif, and Vpr, Env, Tat, and Rev may be selected from other proteins. See, for example: modified gag proteins are described in U.S. Pat. No. 5,972,596. See also, HIV and SIV proteins described in D.H. Barouch et al, J.Virol, 75(5): 2462-. These proteins or subunits thereof may be delivered via multiple vectors or from a single vector, alone or in combination.

Papovaviridae include the sub-family polyomaviridae (BKU and JCU viruses) and the sub-family papillomavirus (associated with cancer or malignant progression of papilloma). The family adenoviridae includes viruses that cause respiratory disease and/or enteritis (EX, AD7, ARD, O.B). Parvoviridae include feline parvovirus (feline enteritis), feline panleukopenia virus, canine parvovirus, and porcine parvoviridae. The herpesviridae family includes the sub-family herpesviridae, which includes the genera herpes simplex virus (HSVI, HSVII), varicella virus (pseudorabies, varicella zoster); and the sub-family of beta herpesviruses, which includes the genus cytomegalovirus (HCMV, murine cytomegalovirus); and the sub-family gamma herpesviridae, which includes the genera lympholatent virus, EBV (burkitt's lymphoma), human herpesviruses 6A, 6B and 7, kaposi's sarcoma-associated herpesviruses and herpes simian viruses (B virus), infectious rhinotracheitis virus, marek's disease virus and parvovirus. The poxviridae include the chordopoxvirinae subfamily, including the orthopoxvirus genus (variola (small pox) and vaccinia (vaccinia)), the parapoxvirus genus, the avipoxvirus genus, the capripoxvirus genus, the leporipoxvirus genus, the suipoxvirus genus, and the entomopoxviridae. Hepadnaviridae includes hepatitis b virus. One of the unclassified viruses that may serve as a suitable source of antigen are hepatitis virus, hepatitis E virus and prion. Another virus that has been used as a source of antigen is the Nipan virus. Other viral sources include avian infectious bursal disease virus and porcine respiratory and reproductive syndrome virus. The family A viruses includes equine arteritis virus and various encephalitis viruses.

The invention also includes immunogens for immunizing human or non-human animals against other pathogens, including bacteria, fungi, parasitic microorganisms or multicellular parasites that infect human and non-human vertebrates, or pathogens derived from cancer cells or tumor cells. Examples of bacterial pathogens include pathogenic gram-positive cocci, including pneumococci, staphylococci (and toxins produced thereby, e.g., enterotoxin B), and streptococci. Pathogenic gram-negative cocci include meningococci, gonococci. Pathogenic enteric gram-negative bacilli include enterobacteriaceae; pseudomonas, acinetobacter, and ekangsiella; pseudomonas melioidis; salmonella; (ii) shigella; haemophilus species: moraxella; haemophilus ducreyi (h. ducreyi) (which causes chancroid); brucellosis (brucellosis); francisella tularensis (Franisella tularensis) harbourne (which causes tularemia); yersinia pestis (plague) and other yersinia species (pasteurella); streptococci moniliforme and spirochetes; gram-positive bacilli including listeria monocytogenes; erysipelothrix rhusiopathiae; corynebacterium diphtheriae (Corynebacterium diphtheria) (diphtheria); cholera; bacillus anthracis (b. anthracosis); donovan disease (groin granuloma) and bartonella disease. Diseases caused by pathogenic anaerobic bacteria include tetanus; botulism (clostridium botulinum and its toxins); clostridium perfringens (Clostridium perfringen) and its toxins; other clostridia species; tuberculosis; leprosy and other mycobacteria. Pathogenic spirochetal diseases including syphilis; dense helical body disease: yase disease, tastain disease and endemic syphilis; and leptospirosis. Other infections caused by more pathogenic bacteria and pathogenic fungi include melioidosis (Burkholderia rhinoceros (Burkholderia melli); actinomycosis; Nocardia disease; cryptococcosis, blastomycosis, histoplasmosis and coccidioidomycosis; candidiasis, aspergillosis and mucormycosis; sporotrichosis; paracoccidioidomycosis, petromycosis, Torulopsis, foot mycosis and chromomycosis; and dermatomycosis Malaria, leishmaniasis, trypanosomiasis, toxoplasmosis, Pneumocystis carinii (Pneumocystis carinii), Trichans, Toxoplasma gondii (Toxoplasma gondii), babesiosis, giardiasis, trichinosis, filariasis, schistosomiasis, nematodes, trematode or fluke (trematode) infections and tapeworm (tapeworm) infections.

Many of these organisms and/or their toxins have been identified by the center for disease control [ (CDC), Department of health and Human Services (usa) ] as materials useful for bioattack. For example, some such biological substances include Bacillus anthracis (anthrax), Clostridium botulinum (Clostridium botulinum) and its toxins (botulinum toxins), Yersinia pestis (Yersinia pestis) (plague), variola major (smallpox), Franisella tularensis (Franisella tularensis), and viral hemorrhagic fever [ filoviruses (e.g., Ebola, Marburg) and arenaviruses [ e.g.: lassa virus, equine papbo virus ]; the Burnetco rickettsia (Coxiella burnetti) (Q fever), Brucella (Brucella disease), Burkholderia mallei (melioidea), Burkholderia mallei (melittis), Burkholderia pseudomallei (melioidea), Burkholderia pseudomallei (Burkholderia pseudomallei), Ricinus communis (Ricinus communis) and its toxin (ricin toxin), Clostridium perfringens (Clostridium perfringens) and its toxin (toxin), Staphylococcus (Staphyloccocus) and its toxin (enterotoxin B), Chlamydia psittaci (psittaci), Theragra, waterborne safety threat (e.g., Vibrio (Vibrio cholera), Cryptosporium parvum (Cryptosporidium parvum), Thermoya maculans (Rituchert virus), and other substances classified as Nipposite, such as Nippon encephalitis, Western encephalitis, and further, such as Nippon encephalitis, and further, as Nippon encephalitis, other organisms so classified or differently classified may also be identified and/or used for such a purpose in the future. It will be readily appreciated that the viral vectors and other constructs described herein may be used to deliver antigens, viruses, toxins or other by-products thereof from such organisms, which may prevent and/or treat infection or other adverse reactions caused by such biological substances.

Administration of the vectors of the invention to deliver immunogens against the variable region of T cells elicits immune responses including CTLs to eliminate T cells. In Rheumatoid Arthritis (RA), several specific TCR variable regions have been identified that are involved in the disease. These TCRs include V-3, V-14, V-17 and V-17. Thus, delivery of a nucleic acid sequence encoding at least one of these polypeptides will elicit an immune response that will target T cells involved in RA. In Multiple Sclerosis (MS), several specific TCR variable regions have been identified that are involved in the disease. These TCRs include V-7 and V-10. Thus, delivery of a nucleic acid sequence encoding at least one of these polypeptides will elicit an immune response that will target T cells involved in MS. In scleroderma, several specific TCR variable regions have been identified that are involved in the disease. These TCRs include V-6, V-8, V-14 and V-16, V-3C, V-7, V-14, V-15, V-16, V-28 and V-12. Thus, delivery of a nucleic acid molecule encoding at least one of these polypeptides will elicit an immune response that targets T cells involved in scleroderma.

Thus, the rAAV-derived recombinant viral vectors of the invention provide an efficient gene transfer vector that can deliver a selected transgene to a selected host cell in vivo or in vitro, even if the organism has neutralizing antibodies to one or more AAV sources. In one embodiment, the rAAV is mixed with the cells in vitro, the infected cells are cultured using conventional methods, and the transduced cells are returned to the patient.

These compositions are particularly useful for gene delivery for therapeutic purposes and for vaccination purposes, including the induction of protective immunity. The AAV of the present invention and compositions comprising the AAV of the present invention may also be used in immunotherapy, such as in U.S. patent application No. 60/565,936, entitled "continuous adenoviral and AAV-mediated delivery of immunogenic molecules", filed 4, 28, 2004, which is common to the applicants of the present application.

In addition, the compositions of the invention may also be used to produce a desired gene product in vitro. For in vitro production, the desired product (e.g., protein) can be obtained as follows: host cells are transfected with a rAAV containing a molecule encoding the desired product, and the cell culture is cultured under conditions that allow expression, and the desired product is then obtained from the culture. The expression product can then be purified and isolated as desired. Suitable transfection, cell culture, purification and isolation techniques are known to those skilled in the art.

The following examples illustrate several aspects and embodiments of the present invention.

Example 1

In accordance with the methods of the present invention, AAV sequences were identified as having a singleton when aligned with a library comprising representative sequences of clade A, B, C, D, E and F (represented by AAV9), respectively. The following table shows the capsid sequences and singleton mutations to be changed to conserved sequences. To indicate some mutations, a single mutation is followed by a sequence of amino acid residues for its substitution. To indicate other mutations, the singleton mutation is followed by its amino acid position and the residue used to replace it.

The amino acid numbering is based on the published sequences of each of these AAV capsids. See, for example: gao et al, j.virol, 78(12):6381-6388 (month 6 2004) and international patent publication No. WO 2004/042397[ all sequences therein are deposited in GenBank ], and international patent publication No. WO 2005/033321 filed on 9/30 2004, which are incorporated herein by reference.

For example, with respect to the following table, the respective names should be understood as follows. Cy5R1 refers to the modified amino acid sequence of SEQ ID NO: 24; at residue 13 of the native amino acid sequence of cy5 is a glycine. Cy5R2 refers to the modified amino acid sequence of SEQ ID NO: 24. cy5R3 has a modified amino acid sequence of SEQ ID NO:24, with the same changes as Cy5R2, and in addition, lysine at position 158 (asparagine in the native sequence) and glutamine at position 161 (proline in the native sequence). In view of the above information, one skilled in the art can readily determine other singleton alterations listed in the following table.

Example 2

In a preliminary study, five clones were selected to test the singleton method of the present invention. The table below provides a phenotypic description of these 5 clones. In addition to predicting the number of singleton mutations, the clade and serotype classes are also indicated.

When the titer is lower than 1X10¹¹At GC, the package phenotype is considered as insufficient; when it is lower than 1X10¹²GCWhen it is, low is asserted; when it is lower than 1X10¹³GC, considered good; higher is considered to be excellent.

Gene transfer phenotype was determined by cb.a1at gene expression and is expressed as follows: "+ + + +", "+" and "-" indicate that more than 50% of the serum concentration level of A1AT compared to the preferred candidate (muscle: AAV1, liver: AAV8, lung: AAV9), corresponding to 10-50% of the level, respectively, is less than 10% of the level. "n/a" indicates that a vector cannot be generated at a sufficient level for in vivo gene transfer studies.

Singleton correction cloning was performed as follows. Site-directed mutagenesis was performed on the original packaging plasmid. After this, the integrity of the vector backbone was determined by Pstl digestion and correction of the singleton was confirmed by sequencing. EGFP-expression vectors were then generated in triplicate in 12-well plates, juxtaposed to parental vector containing the singleton, AAV2, and AAV2/8 positive control production, and production in the absence of packaging plasmid as a negative control. After 3 × freezing, an equal amount of harvested lysate was cultured in 293 cells. eGFP expression was detected by flow cytometry 72 hours after transduction.

Site-directed mutagenesis of the singleton mutations was performed in clones rh.37, rh.2, ch.5, rh.13 and rh.8. These specific sequences were selected to represent the various phenotypes described in the literature previously.

An increase in vector expression was observed in 4 out of 5 clones. The increase in rh.37 and rh.2, which previously showed low packaging yields, was most pronounced. The production level of these carrier-produced particles was sufficient for detection. Vectors rh.8 and rh.13 show an increased transduction rate.

To distinguish the effect of singleton mutations on transduction from the effect on packaging and assembly, small vector preparations were prepared and titrated for Dnase-resistant particles by quantitative PCR. A two-fold log (two-log) increase in vector yield was observed for rh.37. rh.8 showed a 5-fold increase in titer, while rh.13 appeared unchanged. Titers of singleton corrected clones were all within acceptable ranges compared to AAV2 and AAV2/8 products, and when generalized to large scale production. No titration of rh.2 was performed.

The effect of singleton changes was then monitored in vitro in a transduction environment of equal particle number per cell. The titration was performed on rh.8 and rh.13 using 293 cells. The transduction efficiency of all multiplicity of infection (MOI) was moderately increased.

Of this initial subset of 5 clones, 3 were able to transduce cells and had productive capacity. Two clones were unable to produce any eGFP expression in the environment set up in this experiment. This is probably due to some defect in the packaging of the vector which could not be predicted by the singleton method.

The method of the invention was used to correct four predicted singleton mutation sites in AAV clone hu.46: P156S R362C S393F a 676. However, these modifications did not produce AAV that restored its activity, indicating that there were other types of lethal errors in the hu.46 sequence.

Example 3 in vitro analysis of viral vectors with altered capsid

Using the methods of the present invention, the capsid proteins of rh.64 and hu.29 were altered, and then viral vectors with altered capsids were constructed by pseudotyped packaging as described in example 2 and G.Gao et al, Proc Natl Acad Sci, USA, 99, 11854-9 (9.3.2002).

Briefly, the transduction efficiency of vectors in human endothelial kidney cells (293 cells) was tested in vitro using vectors expressing Enhanced Green Fluorescent Protein (EGFP). After a short preincubation with wtAd5, at 10⁴These 293 cells were incubated in the presence of pseudo-type AAVCMVeGFP particles of GC/cells. The number of eGFP-positive cells per 10,000 cells was determined by FACS analysis with a detection sensitivity of 5 cells/10K.

Modifying rh.64 capsids according to the invention provides a 100-fold increase in efficiency of the modified rh.64 particles following a change in R697W. The subsequent V686E mutation increased the packaging capacity by a factor of two.

The hu.29 capsid was modified according to the invention, providing rh.64 viral particles with defective packaging capacity repaired by the change of G396E. It was observed that the increase in virus production was over 1000-fold.

Many of the more than 20 modified AAV viral particles, including AAV6.1, hu.48rr 1, hu.48rr 2, hu.44rr 3, rh.48.2, rh.48.2.1, showed enhanced expression.

Example 4 Effect of mutations in vivo Gene transfer applications

The effect of singleton mutants was studied in an in vivo environment setting. A number of gene transfer studies have been performed with C57B/6 mice on vectors modified according to the methods of the present invention. Muscle and liver orientation studies were initiated and compared on the basis of the preferred candidates currently used for specific applications.

Human alpha-antitrypsin (A1AT) was selected as a sensitive quantitative reporter gene in the vector and expressed under the control of the CMV-enhanced chicken beta-actin promoter. The use of the CB promoter enables high levels of non-tissue specific and constitutive A1AT gene transfer and allows the use of the same vector formulation to study gene transfer in any tissue of interest.

Muscle was selected as the first target tissue. 40 different new vectors (based on 24 different clones each containing the corresponding singleton mutant) were injected intramuscularly into the hind limb of C57B/6 mice. Using CB.A1AT transgene cassette at 1X10¹¹GC/animal was used for all experiments. Each group of each clade used the same amount of vehicle (50. mu.l) per mouse per time. Each independent study included one or two clades and a control group comprising representative serotypes of clades, AAV2/8 and AAV2/1, on which muscle-directed gene transfer was studied. Transgene expression was detected on days 7, 14, 28 and 63 after injection and assessed by a specific hA1AT ELISA.

Performance data was obtained for several isolates and singleton corrections following intrahepatic (intraportal) liver directed injection. Preliminary results indicate that most of the corrected clones performed as well as or better than the original isolate.

For one particular clone, cy.5, singleton correction appears to have a beneficial effect on muscle transduction. The clone cy.5R4, corrected for carrying 4 singletons, had a gene transfer efficiency which was further improved compared to the appropriate muscle tropism already present in the original isolate. The cy.5R4 performed equally or slightly better than the baseline controls AAV2/1 and AAV 2/7.

Isolate rh.64, which previously should have a low titer and could not be evaluated further, performed particularly well in muscle after correction for one singleton. Rh.64R1 performed better than rh.64.2, producing levels of hA1AT higher than its most recent related serotype AAV2/8 and higher than AAV 2/7.

In other studies, mice were injected with vectors based on clade groups. Using the vector for expressing CB.hA1AT at 1X10¹¹GC/mouse dosing. Serum levels of hA1AT were determined using a specific hA1AT ELISA.

The effect of singleton mutations on gene transfer in vivo appears to depend on the isolate and the target tissue. There are several observations that are meaningful.

With respect to certain singleton clones, the effect of singleton is qualitatively similar in muscle and in liver (e.g., rh.2, rh.13, or cy.5). Isolates hu.48 and rh.48 showed that in muscle, expression increased with an increasing number of revertant singletons.

Other clones, such as rh.64 and aav6, showed specific expression characteristics. In the case of isolate hu.48R2, the packaging efficiency was about 10 times lower than that of hu.48R3, but the efficiency of the latter to transduce muscle was about 5 times lower. AAV6 contains two singletons. They all had a moderate effect on packaging, and their combination brought AAV6 packaging to baseline levels. In vitro, the differences between the parental clone and each different clone were almost imperceptible. In vivo, in muscle, AAV6.1 and aav6.1.2 attenuated gene transfer, whereas AAV6.2 enhanced transfer moderately.

Example 5 evaluation of AAV demonstrating mutation-correction in Lung and liver

AAV vectors optimized for packaging and gene transfer efficiency by singleton of mutant residue back mutations were further evaluated in lung and liver. Data are presented for vectors that do not contain singletons and for vectors in which the singletons are reverted to conserved amino acids.

A. Identification of pulmonary metastasis of the CB.A1AT AAV gene mediated by pi2, rh32.33, AAV2/9, AAV2/5, rh.2R, ch5R after intratracheal injection

The ability of several AAV capsids to enter the target, i.e., lung, was compared. The level of cb.a1at in serum was determined. The AAV evaluated had no singleton (pi2, rh32.33, AAV2/9, AAV2/5, rh.2R, ch5R) or contained one singleton (rh.2, rh.8). AAV2/5 and AAV2/9 were referenced.

Gene transfer studies were performed in C57B/6 mice (male, 5 per group) using vectors carrying either the cb.a1at expression cassette (i.e., AAV 25 'ITR, chicken β -actin promoter (CB), human α 1-antitrypsin (A1AT), AAV 23' ITR) or the cb.nlacz expression cassette (i.e., AAV 25 'ITR, nuclear-localized β -galactosidase (nLacZ), AAV 23' ITR) contained in the capsid described above. Briefly, 50. mu.L of singleton-corrected or singleton-free vector was ligated with a vector carrying A1AT and a vector carrying nLacZ (1X 10)¹¹GC) vehicle was co-infused in the gas line (1X 10)¹¹Genomic Copy (GC)).

On days 12 and 20, 20 blood samples were collected, and the serum concentration level of A1AT (ngAAT/mL serum) was determined. And (3) displaying data: at 1X10¹¹Rh.2 to rh.2r significantly increased the expression of human α l-antitrypsin in the lung after GC Intratracheal (IT) injection. In addition, a collection of AAV vectors without single mutation residues was identified. All vectors showed acceptable expression levels in the lung.

B. Assessment of AAV6 singleton vectors compared to AAV2/5 and AAV2/9

The single-site mutation-corrected clone AAV6 was evaluated. Modified AAV6(AAV6.2) was prepared using the singleton mutation correction method of the invention and the pseudotyping techniques described herein. AAV6.2 particles carrying A1AT and LacZ expression cassette were prepared as described in example 5, and intranasally (1X 10)¹¹GC) and endotracheal tube sensationAnd (6) dyeing. AAT expression in serum and bronchoalveolar fluid (BAL) was assessed by ELISA. Normalization was performed based on the expression level of total protein. LacZ expression was determined by ELISA detection of beta-galactosidase in lung homogenates. Necropsy was performed on day 21.

These vectors were compared to AAV2/6, AAV2/5 and AAV2/9 in studies using C57Bl/6 mice (male, n-8/group), AAV2/6 being the current clinical candidate for pulmonary gene transfer.

There was a statistically significant improvement in AAV6.2 over AAV6 in serum A1AT secretion. AAV6.2 also showed higher A1AT levels compared to other vectors, including AAV2/9 and AAV 2/5. In BAL, there was a slight improvement, as was LacZ expression in lung homogenates. However, due to the large animal-to-animal differences, no conclusions can be drawn from LacZ quantification.

When the localization of AAV gene expression was determined, deeper staining of nuclear localization LacZ was observed in AAV2/6.2 group compared to AAV2/6. In the lung airway epithelium, the primary target of diseases such as cystic fibrosis, significant improvements were observed compared to AAV2/6 and AAV 2/5.

C. AAV.CB. A1AT (1X 10) in C57B1/6 mice using clade B and AAV members of clade C¹¹GC) intravenous (iv) injection

All vectors used were free of singleton residues from isolates (AAV2/8, AAV2, hu.13, hu.51, hu.11, hu.53) or by mutation (hu.29R). All vectors were compared to AAV2/8 (clade E) as a benchmark.

D. AVV members of clade E were injected intravenously. The members rh.64Rl, rh.64R2 and rh.2R are optimized by singleton mutation. Other vectors are free of singletons.

It was found that members of AAV clades B and C, including singleton optimized clone hu.29r, expressed approximately comparable to each other. hu.29r was reconstituted from hu.29, reverting to its packaging capacity, and now, it exhibited gene transfer function similar to that of other members of the virus family.

For the clade E vector tested, either the native no-singleton vector or the singleton-corrected vector, performed similarly to the current best vector for liver-targeted gene transfer, AAV 2/8. Of particular note are AAV rh64Rl and rh.64r 2. rh.64 was once thought to be defective in packaging, but now, after one (rh.64rl) or two (rh.64rl 2) singled mutational transitions, its liver-directed gene transfer was equally good. For rh.2, correction for singleton corresponds to a significant increase in gene delivery efficiency of over 10-fold.

All publications, including patents, cited in this specification are herein incorporated by reference. While the invention has been described with reference to a particularly preferred embodiment, it will be understood that modifications may be made without departing from the spirit of the invention.

Sequence listing

<110> Pennsylvania State university Hotel Association

<120> method for enhancing function of adeno-associated virus vector

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<150> US 60/669,083

<151> 2005-04-07

<150> US 60/733,497

<151> 2005-11-04

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<170> PatentIn version 3.3

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Gly Tyr Lys Tyr Leu Gly Pro Phe Asn Gly Leu Asp Lys Gly Glu Pro

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Val Asn Ala Ala Asp Ala Ala Ala Leu Glu His Asp Lys Ala Tyr Asp

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Asp Ala Glu Phe Gln Glu Arg Leu Gln Glu Asp Thr Ser Phe Gly Gly

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Asn Leu Gly Arg Ala Val Phe Gln Ala Lys Lys Arg Val Leu Glu Pro

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Leu Gly Leu Val Glu Glu Gly Ala Lys Thr Ala Pro Gly Lys Lys Arg

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Pro Val Glu Pro Ser Pro Gln Arg Ser Pro Asp Ser Ser Thr Gly Ile

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Gly Lys Thr Gly Gln Gln Pro Ala Lys Lys Arg Leu Asn Phe Gly Gln

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Thr Gly Asp Ser Glu Ser Val Pro Asp Pro Gln Pro Ile Gly Glu Pro

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Pro Ala Gly Pro Ser Gly Leu Gly Ser Gly Thr Met Ala Ala Gly Gly

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Gly Ala Pro Met Ala Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Ser

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Ser Ser Gly Asn Trp His Cys Asp Ser Thr Trp Leu Gly Asp Arg Val

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Ile Thr Thr Ser Thr Arg Thr Trp Ala Leu Pro Thr Tyr Asn Asn His

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Leu Tyr Lys Gln Ile Ser Asn Gly Thr Ser Gly Gly Ser Thr Asn Asp

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Asn Thr Tyr Phe Gly Tyr Ser Thr Pro Trp Gly Tyr Phe Asp Phe Asn

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Arg Phe His Cys His Phe Ser Pro Arg Asp Trp Gln Arg Leu Ile Asn

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Asn Asn Trp Gly Phe Arg Pro Lys Arg Leu Asn Phe Lys Leu Phe Asn

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Ile Gln Val Lys Glu Val Thr Gln Asn Glu Gly Thr Lys Thr Ile Ala

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Asn Asn Leu Thr Ser Thr Ile Gln Val Phe Thr Asp Ser Glu Tyr Gln

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Leu Pro Tyr Val Leu Gly Ser Ala His Gln Gly Cys Leu Pro Pro Phe

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Gln Asn Asn Asn Ser Asn Phe Ala Trp Thr Gly Ala Thr Lys Tyr His

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His Lys Asp Asp Glu Glu Arg Phe Phe Pro Ser Ser Gly Val Leu Met

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His Lys Asp Asp Glu Glu Arg Phe Phe Pro Ser Ser Gly Val Leu Met

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Gly Tyr Lys Tyr Leu Gly Pro Phe Asn Gly Leu Asp Lys Gly Glu Pro

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Ser Ser Gly Asn Trp His Cys Asp Ser Thr Trp Leu Gly Asp Arg Val

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Leu Tyr Lys Gln Ile Ser Asn Gly Thr Ser Gly Gly Ser Thr Asn Asp

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Arg Phe His Cys His Phe Ser Pro Arg Asp Trp Gln Arg Leu Ile Asn

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Asn Asn Trp Gly Phe Arg Pro Lys Arg Leu Ser Phe Lys Leu Phe Asn

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Ile Gln Val Lys Glu Val Thr Gln Asn Glu Gly Thr Lys Thr Ile Ala

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Asn Asn Leu Thr Ser Thr Ile Gln Val Phe Thr Asp Ser Glu Tyr Gln

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Leu Pro Tyr Val Leu Gly Ser Ala His Gln Gly Cys Leu Pro Pro Phe

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Pro Ala Asp Val Phe Met Ile Pro Gln Tyr Gly Tyr Leu Thr Leu Asn

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Asn Gly Ser Gln Ala Val Gly Arg Ser Ser Phe Tyr Cys Leu Glu Tyr

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Phe Pro Ser Gln Met Leu Arg Thr Gly Asn Asn Phe Ser Phe Ser Tyr

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Thr Phe Glu Asp Val Pro Phe His Ser Ser Tyr Ala His Ser Gln Ser

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Leu Asp Arg Leu Met Asn Pro Leu Ile Asp Gln Tyr Leu Tyr Tyr Leu

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Ser Arg Thr Gln Ser Thr Gly Gly Thr Ala Gly Thr Gln Gln Leu Leu

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Phe Ser Gln Ala Gly Pro Ser Asn Met Ser Ala Gln Ala Arg Asn Trp

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Leu Pro Gly Pro Cys Tyr Arg Gln Gln Arg Val Ser Thr Thr Leu Ser

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Gln Asn Asn Asn Ser Asn Phe Ala Trp Thr Gly Ala Thr Lys Tyr His

500 505 510

Leu Asn Gly Arg Asp Ser Leu Val Asn Pro Gly Val Ala Met Ala Thr

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Asn Lys Asp Asp Glu Asp Arg Phe Phe Pro Ser Ser Gly Ile Leu Met

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Phe Gly Lys Gln Gly Ala Gly Lys Asp Asn Val Asp Tyr Ser Asn Val

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Met Leu Thr Ser Glu Glu Glu Ile Lys Ala Thr Asn Pro Val Ala Thr

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Glu Gln Tyr Gly Val Val Ala Asp Asn Leu Gln Gln Gln Asn Thr Ala

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Pro Ile Val Gly Ala Val Asn Ser Gln Gly Ala Leu Pro Gly Met Val

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Trp Gln Asn Arg Asp Val Tyr Leu Gln Gly Pro Ile Trp Ala Lys Ile

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Pro His Thr Asp Gly Asn Phe His Pro Ser Pro Leu Met Gly Gly Phe

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Gly Leu Lys His Pro Pro Pro Gln Ile Leu Ile Lys Asn Thr Pro Val

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Pro Ala Asp Pro Pro Thr Ala Phe Asn Gln Ala Lys Leu Asn Ser Phe

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Ile Thr Gln Tyr Ser Thr Gly Gln Val Ser Val Glu Ile Glu Trp Glu

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Leu Gln Lys Glu Asn Ser Lys Arg Trp Asn Pro Glu Ile Gln Tyr Thr

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<213> macaque adeno-associated virus clone 73 capsid

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Glu Gly Ile Arg Glu Trp Trp Asp Leu Lys Pro Gly Ala Pro Lys Pro

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Lys Ala Asn Gln Gln Lys Gln Asp Asp Gly Arg Gly Leu Val Leu Pro

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Gly Tyr Lys Tyr Leu Gly Pro Phe Asn Gly Leu Asp Lys Gly Glu Pro

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Val Asn Ala Ala Asp Ala Ala Ala Leu Glu His Asp Lys Ala Tyr Asp

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Gln Gln Leu Lys Ala Gly Asp Asn Pro Tyr Leu Arg Tyr Asn His Ala

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Asp Ala Glu Phe Gln Glu Arg Leu Gln Glu Asp Thr Ser Phe Gly Gly

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Asn Leu Gly Arg Ala Val Phe Gln Ala Lys Lys Arg Val Leu Glu Pro

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Leu Gly Leu Val Glu Glu Gly Ala Lys Thr Ala Pro Gly Lys Lys Arg

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Pro Val Glu Pro Ser Pro Gln Arg Ser Pro Asp Ser Ser Thr Gly Ile

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Pro Ala Ala Pro Ser Ser Val Gly Ser Gly Thr Met Ala Ala Gly Gly

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Ser Ser Gly Asn Trp His Cys Asp Ser Thr Trp Leu Gly Asp Arg Val

225 230 235 240

Ile Thr Thr Ser Thr Arg Thr Trp Ala Leu Pro Thr Tyr Asn Asn His

245 250 255

Leu Tyr Lys Gln Ile Ser Asn Gly Thr Ser Gly Gly Ser Thr Asn Asp

260 265 270

Asn Thr Tyr Phe Gly Tyr Ser Thr Pro Trp Gly Tyr Phe Asp Phe Asn

275 280 285

Arg Phe His Cys His Phe Ser Pro Arg Asp Trp Gln Arg Leu Ile Asn

290 295 300

Asn Asn Trp Gly Phe Arg Pro Lys Arg Leu Ser Phe Lys Leu Phe Asn

305 310 315 320

Ile Gln Val Lys Glu Val Thr Gln Asn Glu Gly Thr Lys Thr Ile Ala

325 330 335

Asn Asn Leu Thr Ser Thr Ile Gln Val Phe Thr Asp Ser Glu Tyr Gln

340 345 350

Leu Pro Tyr Val Leu Gly Ser Ala His Gln Gly Cys Leu Pro Pro Phe

355 360 365

Pro Ala Asp Val Phe Met Ile Pro Gln Tyr Gly Tyr Leu Thr Leu Asn

370 375 380

Asn Gly Ser Gln Ala Val Gly Arg Ser Ser Phe Tyr Cys Leu Glu Tyr

385 390 395 400

Phe Pro Ser Gln Met Leu Arg Thr Gly Asn Asn Phe Ser Phe Ser Tyr

405 410 415

Thr Phe Glu Asp Val Pro Phe His Ser Ser Tyr Ala His Ser Gln Ser

420 425 430

Leu Asp Arg Leu Met Asn Pro Leu Ile Asp Gln Tyr Leu Tyr Tyr Leu

435 440 445

Ser Arg Thr Gln Ser Thr Gly Gly Thr Ala Gly Thr Gln Gln Leu Leu

450 455 460

Phe Ser Gln Ala Gly Pro Ser Asn Met Ser Ala Gln Ala Arg Asn Trp

465 470 475 480

Leu Pro Gly Pro Cys Tyr Arg Gln Gln Arg Val Ser Thr Thr Leu Ser

485 490 495

Gln Asn Asn Asn Ser Asn Phe Ala Trp Thr Gly Ala Thr Lys Tyr His

500 505 510

Leu Asn Gly Arg Asp Ser Leu Val Asn Pro Gly Val Ala Met Ala Thr

515 520 525

Asn Lys Asp Asp Glu Asp Arg Phe Phe Pro Ser Ser Gly Ile Leu Met

530 535 540

Phe Gly Lys Gln Gly Ala Gly Lys Asp Asn Val Asp Tyr Ser Asn Val

545 550 555 560

Met Leu Thr Ser Glu Glu Glu Ile Lys Thr Thr Asn Pro Val Ala Thr

565 570 575

Glu Gln Tyr Gly Val Val Ala Asp Asn Leu Gln Arg Gln Asn Thr Ala

580 585 590

Pro Ile Val Gly Ala Val Asn Ser Gln Gly Ala Leu Pro Gly Met Val

595 600 605

Trp Gln Asn Arg Asp Val Tyr Leu Gln Gly Pro Ile Trp Ala Lys Ile

610 615 620

Pro His Thr Asp Gly Asn Phe His Pro Ser Pro Leu Met Gly Gly Phe

625 630 635 640

Gly Leu Lys His Pro Pro Pro Gln Ile Leu Ile Lys Asn Thr Pro Val

645 650 655

Pro Ala Asp Pro Pro Thr Ala Phe Asn Gln Ala Lys Leu Asn Ser Phe

660 665 670

Ile Thr Gln Tyr Ser Thr Gly Gln Val Ser Val Glu Ile Glu Trp Glu

675 680 685

Leu Gln Lys Glu Asn Ser Lys Arg Trp Asn Pro Glu Ile Gln Tyr Thr

690 695 700

Ser Asn Tyr Tyr Lys Ser Thr Asn Val Asp Phe Ala Val Asn Thr Glu

705 710 715 720

Gly Val Tyr Ser Glu Pro Arg Pro Ile Gly Thr Arg Tyr Leu Thr Arg

725 730 735

Asn Leu

<210> 6

<211> 736

<212> PRT

<213> macaque adeno-associated virus clone 74 capsid

<400> 6

Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser

1 5 10 15

Glu Gly Ile Arg Glu Trp Leu Asn Leu Lys Pro Gly Ala Pro Gln Pro

20 25 30

Lys Ala Asn Gln Gln Lys Gln Asp Asn Ala Arg Gly Leu Val Leu Pro

35 40 45

Gly Tyr Lys Tyr Leu Gly Pro Phe Asn Gly Leu Asp Lys Gly Asp Pro

50 55 60

Val Asn Glu Ala Asp Ala Ala Ala Leu Glu His Asp Lys Ala Tyr Gly

65 70 75 80

Gln Gln Leu Lys Ala Gly Asp Asn Pro Tyr Leu Lys Tyr Asn His Ala

85 90 95

Asp Ala Glu Phe Gln Glu Arg Leu Gln Lys Asp Thr Ser Phe Gly Gly

100 105 110

Asn Leu Gly Lys Ala Val Phe Gln Ala Lys Lys Arg Ile Leu Glu Pro

115 120 125

Leu Gly Leu Val Glu Thr Pro Ala Lys Thr Ala Pro Gly Lys Lys Arg

130 135 140

Pro Val Asp Pro Ser Pro Gln Arg Ser Pro Asp Ser Ser Ser Gly Ile

145 150 155 160

Gly Lys Lys Ser Pro His Pro Ala Arg Lys Arg Leu Asn Phe Gly Gln

165 170 175

Thr Gly Glu Ala Glu Ser Val Pro Asp Pro Gln Pro Ile Gly Glu Pro

180 185 190

Pro Ser Asp Pro Ser Ser Val Gly Ser Gly Thr Met Ala Ala Gly Gly

195 200 205

Gly Ala Pro Met Ala Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Asn

210 215 220

Ser Ser Gly Asn Trp His Cys Asp Ser Thr Trp Leu Gly Asp Arg Val

225 230 235 240

Ile Thr Thr Ser Thr Arg Thr Trp Ala Leu Pro Thr Tyr Asn Asn His

245 250 255

Leu Tyr Lys Gln Ile Ser Ser Gln Ser Gly Ala Thr Asn Asp Asn His

260 265 270

Tyr Phe Gly Tyr Ser Thr Pro Trp Gly Tyr Phe Asp Phe Asn Arg Phe

275 280 285

His Cys His Phe Ser Pro Arg Asp Trp Gln Arg Leu Ile Asn Asn Asn

290 295 300

Trp Gly Phe Arg Pro Lys Arg Leu Ser Phe Lys Leu Phe Asn Ile Gln

305 310 315 320

Val Lys Glu Val Thr Gln Asn Asp Gly Thr Thr Thr Ile Ala Asn Asn

325 330 335

Leu Thr Ser Thr Val Gln Val Phe Thr Asp Ser Glu Tyr Gln Leu Pro

340 345 350

Tyr Val Leu Gly Ser Ala His Gln Gly Cys Leu Pro Pro Phe Pro Ala

355 360 365

Asp Val Phe Met Ile Pro Gln Tyr Gly Tyr Leu Thr Leu Asn Asn Gly

370 375 380

Ser Gln Ala Val Gly Arg Ser Ser Phe Tyr Cys Leu Glu Tyr Phe Pro

385 390 395 400

Ser Gln Met Leu Arg Thr Gly Asn Asn Phe Gln Phe Ser Tyr Thr Phe

405 410 415

Glu Asp Val Pro Phe His Ser Ser Tyr Ala His Ser Gln Ser Leu Asp

420 425 430

Arg Leu Met Asn Pro Leu Ile Asp Gln Tyr Leu Tyr Tyr Leu Ser Lys

435 440 445

Thr Gln Gly Thr Asn Ala Thr Val Gln Gly Ala Lys Leu Gln Phe Ser

450 455 460

Gln Ala Gly Pro Ser Asn Met Arg Asp Gln Ala Arg Asn Trp Leu Pro

465 470 475 480

Gly Pro Cys Tyr Arg Gln Gln Arg Val Ser Lys Thr Ala Asn Asp Asn

485 490 495

Asn Asn Ser Glu Tyr Ala Trp Thr Gly Ala Thr Lys Tyr His Leu Asn

500 505 510

Gly Arg Asp Ser Leu Val Asn Pro Gly Pro Ala Met Ala Ser His Lys

515 520 525

Asp Asp Glu Glu Lys Phe Phe Pro Met Asn Gly Thr Leu Val Phe Gly

530 535 540

Lys Asn Gly Ala Gly Asn Ser Asn Val Asp Ile Glu Asn Val Met Ile

545 550 555 560

Thr Asp Glu Glu Glu Ile Arg Thr Thr Asn Pro Val Ala Thr Glu Gln

565 570 575

Tyr Gly Val Val Ser Asp Asn Leu Gln Ser Ser Asn Thr Arg Pro Ile

580 585 590

Thr Gly Asp Val Asp Ser Gln Gly Val Leu Pro Gly Met Val Trp Gln

595 600 605

Asp Arg Asp Val Tyr Leu Gln Gly Pro Ile Trp Ala Lys Ile Pro His

610 615 620

Thr Asp Gly His Phe His Pro Ser Pro Leu Met Gly Gly Phe Gly Leu

625 630 635 640

Lys His Pro Pro Pro Gln Ile Leu Ile Lys Asn Thr Pro Val Pro Ala

645 650 655

Asn Pro Ala Thr Thr Phe Thr Pro Gly Lys Phe Ala Ser Phe Ile Thr

660 665 670

Gln Tyr Ser Thr Gly Gln Val Ser Val Gln Ile Glu Trp Glu Leu Gln

675 680 685

Lys Glu Asn Ser Lys Arg Trp Asn Pro Glu Ile Gln Tyr Thr Ser Asn

690 695 700

Tyr Asn Lys Ser Val Asn Val Asp Phe Thr Val Asp Thr Asn Gly Val

705 710 715 720

Tyr Ser Glu Pro Arg Pro Ile Gly Thr Arg Tyr Leu Thr Arg Asn Leu

725 730 735

<210> 7

<211> 2208

<212> DNA

<213> adeno-associated Virus serotype 2

<400> 7

atggctgccg atggttatct tccagattgg ctcgaggaca ctctctctga aggaataaga 60

cagtggtgga agctcaaacc tggcccacca ccaccaaagc ccgcagagcg gcataaggac 120

gacagcaggg gtcttgtgct tcctgggtac aagtacctcg gacccttcaa cggactcgac 180

aagggagagc cggtcaacga ggcagacgcc gcggccctcg agcacgacaa agcctacgac 240

cggcagctcg acagcggaga caacccgtac ctcaagtaca accacgccga cgcggagttt 300

caggagcgcc ttaaagaaga tacgtctttt gggggcaacc tcggacgagc agtcttccag 360

gcgaaaaaga gggttcttga acctctgggc ctggttgagg aacctgttaa gacggctccg 420

ggaaaaaaga ggccggtaga gcactctcct gtggagccag actcctcctc gggaaccgga 480

aaggcgggcc agcagcctgc aagaaaaaga ttgaattttg gtcagactgg agacgcagac 540

tcagtacctg acccccagcc tctcggacag ccaccagcag ccccctctgg tctgggaact 600

aatacgatgg ctacaggcag tggcgcacca atggcagaca ataacgaggg cgccgacgga 660

gtgggtaatt cctcgggaaa ttggcattgc gattccacat ggatgggcga cagagtcatc 720

accaccagca cccgaacctg ggccctgccc acctacaaca accacctcta caaacaaatt 780

tccagccaat caggagcctc gaacgacaat cactactttg gctacagcac cccttggggg 840

tattttgact tcaacagatt ccactgccac ttttcaccac gtgactggca aagactcatc 900

aacaacaact ggggattccg acccaagaga ctcaacttca agctctttaa cattcaagtc 960

aaagaggtca cgcagaatga cggtacgacg acgattgcca ataaccttac cagcacggtt 1020

caggtgttta ctgactcgga gtaccagctc ccgtacgtcc tcggctcggc gcatcaagga 1080

tgcctcccgc cgttcccagc agacgtcttc atggtgccac agtatggata cctcaccctg 1140

aacaacggga gtcaggcagt aggacgctct tcattttact gcctggagta ctttccttct 1200

cagatgctgc gtaccggaaa caactttacc ttcagctaca cttttgagga cgttcctttc 1260

cacagcagct acgctcacag ccagagtctg gaccgtctca tgaatcctct catcgaccag 1320

tacctgtatt acttgagcag aacaaacact ccaagtggaa ccaccacgca gtcaaggctt 1380

cagttttctc aggccggagc gagtgacatt cgggaccagt ctaggaactg gcttcctgga 1440

ccctgttacc gccagcagcg agtatcaaag acatctgcgg ataacaacaa cagtgaatac 1500

tcgtggactg gagctaccaa gtaccacctc aatggcagag actctctggt gaatccgggc 1560

ccggccatgg caagccacaa ggacgatgaa gaaaagtttt ttcctcagag cggggttctc 1620

atctttggga agcaaggctc agagaaaaca aatgtggaca ttgaaaaggt catgattaca 1680

gacgaagagg aaatcaggac aaccaatccc gtggctacgg agcagtatgg ttctgtatct 1740

accaacctcc agagaggcaa cagacaagca gctaccgcag atgtcaacac acaaggcgtt 1800

cttccaggca tggtctggca ggacagagat gtgtaccttc aggggcccat ctgggcaaag 1860

attccacaca cggacggaca ttttcacccc tctcccctca tgggtggatt cggacttaaa 1920

caccctcctc cacagattct catcaagaac accccggtac ctgcgaatcc ttcgaccacc 1980

ttcagtgcgg caaagtttgc ttccttcatc acacagtact ccacgggaca ggtcagcgtg 2040

gagatcgagt gggagctgca gaaggaaaac agcaaacgct ggaatcccga aattcagtac 2100

acttccaact acaacaagtc tgttaatgtg gactttactg tggacactaa tggcgtgtat 2160

tcagagcctc gccccattgg caccagatac ctgactcgta atctgtaa 2208

<210> 8

<211> 2187

<212> DNA

<213> cy.5 nucleic acids

<400> 8

atggctgccg atggttatct tccagattgg ctcgagggca acctctctga gggcattcgc 60

gagtggtggg acttgaaacc tggagccccg aaacccaaag ccaaccagca aaagcaggac 120

gacggccggg gtctggtgct tcctggctac aggtacctcg gacccttcaa cggactcgac 180

aagggagagc cggtcaacga ggcagacgcc gcggccctcg agcacgacaa ggcctacgac 240

aagcagctcg agcaggggga caacccgtac ctcaagtaca accacgccga cgccgagttt 300

caggagcgtc ttcaagaaga tacgtctttt gggggcaacc tcgggcgagc agtcttccag 360

gccaagaagc gggttctcga acctctcggt ctggttgagg aaggcgctaa gacggctcct 420

ggaaagaaga gacccataga atcccccgac tcctccacgg gcatcggcaa gaacggccag 480

ccgcccgcta aaaagaagct caactttggg cagactggcg actcagagtc agtgcccgac 540

ccccaacctc tcggagaacc tcccgccgcg ccctcaggtc tgggatctgg tacaatggct 600

gcaggcggtg gcgcaccaat ggcagacaat aacgaaggcg ccgacggagt gggtaatgcc 660

tccggaaatt ggcattgcga ttccacatgg ctgggcgaca gagtcatcac caccagcacc 720

cgcacctggg ccctgcccac ctacaacaac cacctctaca agcagatatc aagtcagagc 780

ggggctacca acgacaacca cttcttcggc tacagcaccc cctggggcta ttttgacttc 840

aacagattcc actgccactt ctcaccacgt gactggcagc gactcatcaa caacaactgg 900

ggattccggc ccagaaagct gcggttcaag ttgttcaaca tccaggtcaa ggaggtcacg 960

acgaacgacg gcgttacgac catcgctaat aaccttacca gcacgattca ggtcttctcg 1020

gactcggagt accaactgcc gtacgtcctc ggctctgcgc accagggctg cctccctccg 1080

ttccctgcgg acgtgttcat gattcctcag tacggatatc tgactctaaa caacggcagt 1140

cagtctgtgg gacgttcctc cttctactgc ctggagtact ttccttctca gatgctgaga 1200

acgggcgata actttgaatt cagctacacc tttgaggaag tgcctttcca cagcagctat 1260

gcgcacagcc agagcctgga ccggctgatg aatcccctca tcgaccagta cctgtactac 1320

ctggcccgga cccagagcac tacggggtcc acaagggagc tgcagttcca tcaggctggg 1380

cccaacacca tggccgagca atcaaagaac tggctgcccg gaccctgtta tcggcagcag 1440

agactgtcaa aaaacataga cagcaacaac aacagtaact ttgcctggac cggggccact 1500

aaataccatc tgaatggtag aaattcatta accaacccgg gcgtagccat ggccaccaac 1560

aaggacgacg aggaccagtt ctttcccatc aacggagtgc tggtttttgg caaaacgggg 1620

gctgccaaca agacaacgct ggaaaacgtg ctaatgacca gcgaggagga gatcaaaacc 1680

accaatcccg tggctacaga agaatacggt gtggtctcca gcaacctgca atcgtctacg 1740

gccggacccc agacacagac tgtcaacagc cagggggctc tgcccggcat ggtctggcag 1800

aaccgggacg tgtacctgca gggtcccatc tgggccaaaa ttcctcacac ggacggcaac 1860

tttcacccgt ctcccctgat gggcggattt ggactcaaac acccgcctcc tcaaattctc 1920

atcaaaaaca ccccggtacc tgctaatcct ccagaggtgt ttactcctgc caagtttgcc 1980

tcatttatca cgcagtacag caccggccag gtcagcgtgg agatcgagtg ggaactgcag 2040

aaagaaaaca gcaaacgctg gaatccagag attcagtaca cctcaaatta tgccaagtct 2100

aataatgtgg aatttgctgt caacaacgaa ggggtttata ctgagcctcg ccccattggc 2160

acccgttacc tcacccgtaa cctgtaa 2187

<210> 9

<211> 2217

<212> DNA

<213> macaque gland-associated Virus, rh.10

<400> 9

atggctgccg atggttatct tccagattgg ctcgaggaca acctctctga gggcattcgc 60

gagtggtggg acttgaaacc tggagccccg aaacccaaag ccaaccagca aaagcaggac 120

gacggccggg gtctggtgct tcctggctac aagtacctcg gacccttcaa cggactcgac 180

aagggggagc ccgtcaacgc ggcggacgca gcggccctcg agcacgacaa ggcctacgac 240

cagcagctca aagcgggtga caatccgtac ctgcggtata accacgccga cgccgagttt 300

caggagcgtc tgcaagaaga tacgtctttt gggggcaacc tcgggcgagc agtcttccag 360

gccaagaagc gggttctcga acctctcggt ctggttgagg aaggcgctaa gacggctcct 420

ggaaagaaga gaccggtaga gccatcaccc cagcgttctc cagactcctc tacgggcatc 480

ggcaagaaag gccagcagcc cgcgaaaaag agactcaact ttgggcagac tggcgactca 540

gagtcagtgc ccgaccctca accaatcgga gaaccccccg caggcccctc tggtctggga 600

tctggtacaa tggctgcagg cggtggcgct ccaatggcag acaataacga aggcgccgac 660

ggagtgggta gttcctcagg aaattggcat tgcgattcca catggctggg cgacagagtc 720

atcaccacca gcacccgaac ctgggccctc cccacctaca acaaccacct ctacaagcaa 780

atctccaacg ggacttcggg aggaagcacc aacgacaaca cctacttcgg ctacagcacc 840

ccctgggggt attttgactt taacagattc cactgccact tctcaccacg tgactggcag 900

cgactcatca acaacaactg gggattccgg cccaagagac tcaacttcaa gctcttcaac 960

atccaggtca aggaggtcac gcagaatgaa ggcaccaaga ccatcgccaa taaccttacc 1020

agcacgattc aggtctttac ggactcggaa taccagctcc cgtacgtcct cggctctgcg 1080

caccagggct gcctgcctcc gttcccggcg gacgtcttca tgattcctca gtacgggtac 1140

ctgactctga acaatggcag tcaggccgtg ggccgttcct ccttctactg cctggagtac 1200

tttccttctc aaatgctgag aacgggcaac aactttgagt tcagctacca gtttgaggac 1260

gtgccttttc acagcagcta cgcgcacagc caaagcctgg accggctgat gaaccccctc 1320

atcgaccagt acctgtacta cctgtctcgg actcagtcca cgggaggtac cgcaggaact 1380

cagcagttgc tattttctca ggccgggcct aataacatgt cggctcaggc caaaaactgg 1440

ctacccgggc cctgctaccg gcagcaacgc gtctccacga cactgtcgca aaataacaac 1500

agcaactttg cctggaccgg tgccaccaag tatcatctga atggcagaga ctctctggta 1560

aatcccggtg tcgctatggc aacccacaag gacgacgaag agcgattttt tccgtccagc 1620

ggagtcttaa tgtttgggaa acagggagct ggaaaagaca acgtggacta tagcagcgtt 1680

atgctaacca gtgaggaaga aattaaaacc accaacccag tggccacaga acagtacggc 1740

gtggtggccg ataacctgca acagcaaaac gccgctccta ttgtaggggc cgtcaacagt 1800

caaggagcct tacctggcat ggtctggcag aaccgggacg tgtacctgca gggtcctatc 1860

tgggccaaga ttcctcacac ggacggaaac tttcatccct cgccgctgat gggaggcttt 1920

ggactgaaac acccgcctcc tcagatcctg attaagaata cacctgttcc cgcggatcct 1980

ccaactacct tcagtcaagc taagctggcg tcgttcatca cgcagtacag caccggacag 2040

gtcagcgtgg aaattgaatg ggagctgcag aaagaaaaca gcaaacgctg gaacccagag 2100

attcaataca cttccaacta ctacaaatct acaaatgtgg actttgctgt taacacagat 2160

ggcacttatt ctgagcctcg ccccatcggc acccgttacc tcacccgtaa tctgtaa 2217

<210> 10

<211> 2187

<212> DNA

<213> Actinidia adeno-associated virus, rh.13

<400> 10

atggctgccg atggttatct tccagattgg ctcgaggaca acctctctga gggcattcgc 60

gagtggtggg acttgaaacc tggagccccg aaacccaaag ccaaccagca aaagcaggac 120

gacggccggg gtctggtgct tcctggctac aagtacctcg gacccttcaa cggactcgac 180

aagggagagc cggtcaacga ggcagacgcc gcggccctcg agcacgacaa ggcctacgac 240

aagcagctcg agcaggggga caacccgtac ctcaagtaca accacgccga cgccgagttt 300

caggagcgtc ttcaagaaga tacgtctttt gggggcaacc tcgggcgagc agtcttccag 360

gccaagaagc gggttctcga acctctcggt ctggttgagg aaggcgctaa gacggctcct 420

ggaaagaaga gacccataga atcccccgac tcctccacgg gcatcggcaa gaaaggccag 480

cagcccgcta aaaagaagct caactttggg cagactggcg actcagagtc agtgcccgac 540

ccccaacctc tcggagaacc tcccgccgcg ccctcaggtc tgggatctgg tacaatggct 600

gcaggcggtg gcgcaccaat ggcagacaat aacgaaggcg ccgacggagt gggtaatgcc 660

tccggaaatt ggcattgcga ttccacatgg ctgggcgaca gagtcatcac caccagcacc 720

cgcacctggg ccctgcccac ctacaacaac cacctctaca agcagatatc aagtcagagc 780

ggggctacca acgacaacca cttcttcggc tacagcaccc cctggggcta ttttgacttc 840

aacagattcc actgccactt ctcaccacgt gactggcagc gactcatcaa caacaactgg 900

ggattccggc ccagaaagct gcggttcaag ttgttcaaca tccaggtcaa ggaggtcacg 960

acgaacgacg gcgttacgac catcgctaat aaccttacca gcacgattca ggtcttctcg 1020

gactcggagt accaactgcc gtacgtcctc ggctctgcgc accagggctg cctccctccg 1080

ttccctgcgg acgtgttcat gattcctcag tacggatatc tgactctaaa caacggcagt 1140

cagtctgtgg gacgttcctc cttctactgc ctggagtact ttccttctca gatgctgaga 1200

acgggcaata actttgaatt cagctacacc tttgaggaag tgcctttcca cagcagctat 1260

gcgcacagcc agagcctgga ccggctgatg aatcccctca tcgaccagta cctgtactac 1320

ctggcccgga cccagagcac tacggggtcc acaagggagc tgcagttcca tcaggctggg 1380

cccaacacca tggccgagca atcaaagaac tggctgcccg gaccctgtta tcggcagcag 1440

agactgtcaa aaaacataga cagcaacaac aacagtaact ttgcctggac cggggccact 1500

aaataccatc tgaatggtag aaattcatta accaacccgg gcgtagccat ggccaccaac 1560

aaggacgacg aggaccagtt ctttcccatc aacggagtgc tggtttttgg cgaaacgggg 1620

gctgccaaca agacaacgct ggaaaacgtg ctaatgacca gcgaggagga gatcaaaacc 1680

accaatcccg tggctacaga agaatacggt gtggtctcca gcaacctgca atcgtctacg 1740

gccggacccc agacacagac tgtcaacagc cagggggctc tgcccggcat ggtctggcag 1800

aaccgggacg tgtacctgca gggtcccatc tgggccaaaa ttcctcacac ggacggcaac 1860

tttcacccgt ctcccctgat gggcggattt ggactcaaac acccgcctcc tcaaattctc 1920

atcaaaaaca ccccggtacc tgctaatcct ccagaggtgt ttactcctgc caagtttgcc 1980

tcatttatca cgcagtacag caccggccag gtcagcgtgg agatcgagtg ggaactgcag 2040

aaagaaaaca gcaaacgctg gaatccagag attcagtaca cctcaaatta tgccaagtct 2100

aataatgtgg aatttgctgt caacaacgaa ggggtttata ctgagcctcg ccccattggc 2160

acccgttacc tcacccgtaa cctgtaa 2187

<210> 11

<211> 2211

<212> DNA

<213> adeno-associated Virus serotype 1

<400> 11

atggctgccg atggttatct tccagattgg ctcgaggaca acctctctga gggcattcgc 60

gagtggtggg acttgaaacc tggagccccg aagcccaaag ccaaccagca aaagcaggac 120

gacggccggg gtctggtgct tcctggctac aagtacctcg gacccttcaa cggactcgac 180

aagggggagc ccgtcaacgc ggcggacgca gcggccctcg agcacgacaa ggcctacgac 240

cagcagctca aagcgggtga caatccgtac ctgcggtata accacgccga cgccgagttt 300

caggagcgtc tgcaagaaga tacgtctttt gggggcaacc tcgggcgagc agtcttccag 360

gccaagaagc gggttctcga acctctcggt ctggttgagg aaggcgctaa gacggctcct 420

ggaaagaaac gtccggtaga gcagtcgcca caagagccag actcctcctc gggcatcggc 480

aagacaggcc agcagcccgc taaaaagaga ctcaattttg gtcagactgg cgactcagag 540

tcagtccccg atccacaacc tctcggagaa cctccagcaa cccccgctgc tgtgggacct 600

actacaatgg cttcaggcgg tggcgcacca atggcagaca ataacgaagg cgccgacgga 660

gtgggtaatg cctcaggaaa ttggcattgc gattccacat ggctgggcga cagagtcatc 720

accaccagca cccgcacctg ggccttgccc acctacaata accacctcta caagcaaatc 780

tccagtgctt caacgggggc cagcaacgac aaccactact tcggctacag caccccctgg 840

gggtattttg atttcaacag attccactgc cacttttcac cacgtgactg gcagcgactc 900

atcaacaaca attggggatt ccggcccaag agactcaact tcaaactctt caacatccaa 960

gtcaaggagg tcacgacgaa tgatggcgtc acaaccatcg ctaataacct taccagcacg 1020

gttcaagtct tctcggactc ggagtaccag cttccgtacg tcctcggctc tgcgcaccag 1080

ggctgcctcc ctccgttccc ggcggacgtg ttcatgattc cgcaatacgg ctacctgacg 1140

ctcaacaatg gcagccaagc cgtgggacgt tcatcctttt actgcctgga atatttccct 1200

tctcagatgc tgagaacggg caacaacttt accttcagct acacctttga ggaagtgcct 1260

ttccacagca gctacgcgca cagccagagc ctggaccggc tgatgaatcc tctcatcgac 1320

caatacctgt attacctgaa cagaactcaa aatcagtccg gaagtgccca aaacaaggac 1380

ttgctgttta gccgtgggtc tccagctggc atgtctgttc agcccaaaaa ctggctacct 1440

ggaccctgtt atcggcagca gcgcgtttct aaaacaaaaa cagacaacaa caacagcaat 1500

tttacctgga ctggtgcttc aaaatataac ctcaatgggc gtgaatccat catcaaccct 1560

ggcactgcta tggcctcaca caaagacgac gaagacaagt tctttcccat gagcggtgtc 1620

atgatttttg gaaaagagag cgccggagct tcaaacactg cattggacaa tgtcatgatt 1680

acagacgaag aggaaattaa agccactaac cctgtggcca ccgaaagatt tgggaccgtg 1740

gcagtcaatt tccagagcag cagcacagac cctgcgaccg gagatgtgca tgctatggga 1800

gcattacctg gcatggtgtg gcaagataga gacgtgtacc tgcagggtcc catttgggcc 1860

aaaattcctc acacagatgg acactttcac ccgtctcctc ttatgggcgg ctttggactc 1920

aagaacccgc ctcctcagat cctcatcaaa aacacgcctg ttcctgcgaa tcctccggcg 1980

gagttttcag ctacaaagtt tgcttcattc atcacccaat actccacagg acaagtgagt 2040

gtggaaattg aatgggagct gcagaaagaa aacagcaagc gctggaatcc cgaagtgcag 2100

tacacatcca attatgcaaa atctgccaac gttgatttta ctgtggacaa caatggactt 2160

tatactgagc ctcgccccat tggcacccgt taccttaccc gtcccctgta a 2211

<210> 12

<211> 2211

<212> DNA

<213> adeno-associated Virus serotype 3

<400> 12

atggctgctg acggttatct tccagattgg ctcgaggaca acctttctga aggcattcgt 60

gagtggtggg ctctgaaacc tggagtccct caacccaaag cgaaccaaca acaccaggac 120

aaccgtcggg gtcttgtgct tccgggttac aaatacctcg gacccggtaa cggactcgac 180

aaaggagagc cggtcaacga ggcggacgcg gcagccctcg aacacgacaa agcttacgac 240

cagcagctca aggccggtga caacccgtac ctcaagtaca accacgccga cgccgagttt 300

caggagcgtc ttcaagaaga tacgtctttt gggggcaacc ttggcagagc agtcttccag 360

gccaaaaaga ggatccttga gcctcttggt ctggttgagg aagcagctaa aacggctcct 420

ggaaagaagg gggctgtaga tcagtctcct caggaaccgg actcatcatc tggtgttggc 480

aaatcgggca aacagcctgc cagaaaaaga ctaaatttcg gtcagactgg agactcagag 540

tcagtcccag accctcaacc tctcggagaa ccaccagcag cccccacaag tttgggatct 600

aatacaatgg cttcaggcgg tggcgcacca atggcagaca ataacgaggg tgccgatgga 660

gtgggtaatt cctcaggaaa ttggcattgc gattcccaat ggctgggcga cagagtcatc 720

accaccagca ccagaacctg ggccctgccc acttacaaca accatctcta caagcaaatc 780

tccagccaat caggagcttc aaacgacaac cactactttg gctacagcac cccttggggg 840

tattttgact ttaacagatt ccactgccac ttctcaccac gtgactggca gcgactcatt 900

aacaacaact ggggattccg gcccaagaaa ctcagcttca agctcttcaa catccaagtt 960

agaggggtca cgcagaacga tggcacgacg actattgcca ataaccttac cagcacggtt 1020

caagtgttta cggactcgga gtatcagctc ccgtacgtgc tcgggtcggc gcaccaaggc 1080

tgtctcccgc cgtttccagc ggacgtcttc atggtccctc agtatggata cctcaccctg 1140

aacaacggaa gtcaagcggt gggacgctca tccttttact gcctggagta cttcccttcg 1200

cagatgctaa ggactggaaa taacttccaa ttcagctata ccttcgagga tgtacctttt 1260

cacagcagct acgctcacag ccagagtttg gatcgcttga tgaatcctct tattgatcag 1320

tatctgtact acctgaacag aacgcaagga acaacctctg gaacaaccaa ccaatcacgg 1380

ctgcttttta gccaggctgg gcctcagtct atgtctttgc aggccagaaa ttggctacct 1440

gggccctgct accggcaaca gagactttca aagactgcta acgacaacaa caacagtaac 1500

tttccttgga cagcggccag caaatatcat ctcaatggcc gcgactcgct ggtgaatcca 1560

ggaccagcta tggccagtca caaggacgat gaagaaaaat ttttccctat gcacggcaat 1620

ctaatatttg gcaaagaagg gacaacggca agtaacgcag aattagataa tgtaatgatt 1680

acggatgaag aagagattcg taccaccaat cctgtggcaa cagagcagta tggaactgtg 1740

gcaaataact tgcagagctc aaatacagct cccacgactg gaactgtcaa tcatcagggg 1800

gccttacctg gcatggtgtg gcaagatcgt gacgtgtacc ttcaaggacc tatctgggca 1860

aagattcctc acacggatgg acactttcat ccttctcctc tgatgggagg ctttggactg 1920

aaacatccgc ctcctcaaat catgatcaaa aatactccgg taccggcaaa tcctccgacg 1980

actttcagcc cggccaagtt tgcttcattt atcactcagt actccactgg acaggtcagc 2040

gtggaaattg agtgggagct acagaaagaa aacagcaaac gttggaatcc agagattcag 2100

tacacttcca actacaacaa gtctgttaat gtggacttta ctgtagacac taatggtgtt 2160

tatagtgaac ctcgccctat tggaacccgg tatctcacac gaaacttgtg a 2211

<210> 13

<211> 2208

<212> DNA

<213> adeno-associated Virus serotype 6

<400> 13

atggctgccg atggttatct tccagattgg ctcgaggaca acctctctga gggcattcgc 60

gagtggtggg acttgaaacc tggagccccg aaacccaaag ccaaccagca aaagcaggac 120

gacggccggg gtctggtgct tcctggctac aagtacctcg gacccttcaa cggactcgac 180

aagggggagc ccgtcaacgc ggcggatgca gcggccctcg agcacgacaa ggcctacgac 240

cagcagctca aagcgggtga caatccgtac ctgcggtata accacgccga cgccgagttt 300

caggagcgtc tgcaagaaga tacgtctttt gggggcaacc tcgggcgagc agtcttccag 360

gccaagaaga gggttctcga accttttggt ctggttgagg aaggtgctaa gacggctcct 420

ggaaagaaac gtccggtaga gcagtcgcca caagagccag actcctcctc gggcattggc 480

aagacaggcc agcagcccgc taaaaagaga ctcaattttg gtcagactgg cgactcagag 540

tcagtccccg acccacaacc tctcggagaa cctccagcaa cccccgctgc tgtgggacct 600

actacaatgg cttcaggcgg tggcgcacca atggcagaca ataacgaagg cgccgacgga 660

gtgggtaatg cctcaggaaa ttggcattgc gattccacat ggctgggcga cagagtcatc 720

accaccagca cccgaacatg ggccttgccc acctataaca accacctcta caagcaaatc 780

tccagtgctt caacgggggc cagcaacgac aaccactact tcggctacag caccccctgg 840

gggtattttg atttcaacag attccactgc catttctcac cacgtgactg gcagcgactc 900

atcaacaaca attggggatt ccggcccaag agactcaact tcaagctctt caacatccaa 960

gtcaaggagg tcacgacgaa tgatggcgtc acgaccatcg ctaataacct taccagcacg 1020

gttcaagtct tctcggactc ggagtaccag ttgccgtacg tcctcggctc tgcgcaccag 1080

ggctgcctcc ctccgttccc ggcggacgtg ttcatgattc cgcagtacgg ctacctaacg 1140

ctcaacaatg gcagccaggc agtgggacgg tcatcctttt actgcctgga atatttccca 1200

tcgcagatgc tgagaacggg caataacttt accttcagct acaccttcga ggacgtgcct 1260

ttccacagca gctacgcgca cagccagagc ctggaccggc tgatgaatcc tctcatcgac 1320

cagtacctgt attacctgaa cagaactcag aatcagtccg gaagtgccca aaacaaggac 1380

ttgctgttta gccgggggtc tccagctggc atgtctgttc agcccaaaaa ctggctacct 1440

ggaccctgtt accggcagca gcgcgtttct aaaacaaaaa cagacaacaa caacagcaac 1500

tttacctgga ctggtgcttc aaaatataac cttaatgggc gtgaatctat aatcaaccct 1560

ggcactgcta tggcctcaca caaagacgac aaagacaagt tctttcccat gagcggtgtc 1620

atgatttttg gaaaggagag cgccggagct tcaaacactg cattggacaa tgtcatgatc 1680

acagacgaag aggaaatcaa agccactaac cccgtggcca ccgaaagatt tgggactgtg 1740

gcagtcaatc tccagagcag cagcacagac cctgcgaccg gagatgtgca tgttatggga 1800

gccttacctg gaatggtgtg gcaagacaga gacgtatacc tgcagggtcc tatttgggcc 1860

aaaattcctc acacggatgg acactttcac ccgtctcctc tcatgggcgg ctttggactt 1920

aagcacccgc ctcctcagat cctcatcaaa aacacgcctg ttcctgcgaa tcctccggca 1980

gagttttcgg ctacaaagtt tgcttcattc atcacccagt attccacagg acaagtgagc 2040

gtggagattg aatgggagct gcagaaagaa aacagcaaac gctggaatcc cgaagtgcag 2100

tatacatcta actatgcaaa atctgccaac gttgatttca ctgtggacaa caatggactt 2160

tatactgagc ctcgccccat tggcacccgt tacctcaccc gtcccctg 2208

<210> 14

<211> 2214

<212> DNA

<213> adeno-associated Virus serotype 7

<400> 14

atggctgccg atggttatct tccagattgg ctcgaggaca acctctctga gggcattcgc 60

gagtggtggg acctgaaacc tggagccccg aaacccaaag ccaaccagca aaagcaggac 120

aacggccggg gtctggtgct tcctggctac aagtacctcg gacccttcaa cggactcgac 180

aagggggagc ccgtcaacgc ggcggacgca gcggccctcg agcacgacaa ggcctacgac 240

cagcagctca aagcgggtga caatccgtac ctgcggtata accacgccga cgccgagttt 300

caggagcgtc tgcaagaaga tacgtcattt gggggcaacc tcgggcgagc agtcttccag 360

gccaagaagc gggttctcga acctctcggt ctggttgagg aaggcgctaa gacggctcct 420

gcaaagaaga gaccggtaga gccgtcacct cagcgttccc ccgactcctc cacgggcatc 480

ggcaagaaag gccagcagcc cgccagaaag agactcaatt tcggtcagac tggcgactca 540

gagtcagtcc ccgaccctca acctctcgga gaacctccag cagcgccctc tagtgtggga 600

tctggtacag tggctgcagg cggtggcgca ccaatggcag acaataacga aggtgccgac 660

ggagtgggta atgcctcagg aaattggcat tgcgattcca catggctggg cgacagagtc 720

attaccacca gcacccgaac ctgggccctg cccacctaca acaaccacct ctacaagcaa 780

atctccagtg aaactgcagg tagtaccaac gacaacacct acttcggcta cagcaccccc 840

tgggggtatt ttgactttaa cagattccac tgccacttct caccacgtga ctggcagcga 900

ctcatcaaca acaactgggg attccggccc aagaagctgc ggttcaagct cttcaacatc 960

caggtcaagg aggtcacgac gaatgacggc gttacgacca tcgctaataa ccttaccagc 1020

acgattcagg tattctcgga ctcggaatac cagctgccgt acgtcctcgg ctctgcgcac 1080

cagggctgcc tgcctccgtt cccggcggac gtcttcatga ttcctcagta cggctacctg 1140

actctcaaca atggcagtca gtctgtggga cgttcctcct tctactgcct ggagtacttc 1200

ccctctcaga tgctgagaac gggcaacaac tttgagttca gctacagctt cgaggacgtg 1260

cctttccaca gcagctacgc acacagccag agcctggacc ggctgatgaa tcccctcatc 1320

gaccagtact tgtactacct ggccagaaca cagagtaacc caggaggcac agctggcaat 1380

cgggaactgc agttttacca gggcgggcct tcaactatgg ccgaacaagc caagaattgg 1440

ttacctggac cttgcttccg gcaacaaaga gtctccaaaa cgctggatca aaacaacaac 1500

agcaactttg cttggactgg tgccaccaaa tatcacctga acggcagaaa ctcgttggtt 1560

aatcccggcg tcgccatggc aactcacaag gacgacgagg accgcttttt cccatccagc 1620

ggagtcctga tttttggaaa aactggagca actaacaaaa ctacattgga aaatgtgtta 1680

atgacaaatg aagaagaaat tcgtcctact aatcctgtag ccacggaaga atacgggata 1740

gtcagcagca acttacaagc ggctaatact gcagcccaga cacaagttgt caacaaccag 1800

ggagccttac ctggcatggt ctggcagaac cgggacgtgt acctgcaggg tcccatctgg 1860

gccaagattc ctcacacgga tggcaacttt cacccgtctc ctttgatggg cggctttgga 1920

cttaaacatc cgcctcctca gatcctgatc aagaacactc ccgttcccgc taatcctccg 1980

gaggtgttta ctcctgccaa gtttgcttcg ttcatcacac agtacagcac cggacaagtc 2040

agcgtggaaa tcgagtggga gctgcagaag gaaaacagca agcgctggaa cccggagatt 2100

cagtacacct ccaactttga aaagcagact ggtgtggact ttgccgttga cagccagggt 2160

gtttactctg agcctcgccc tattggcact cgttacctca cccgtaatct gtaa 2214

<210> 15

<211> 2217

<212> DNA

<213> adeno-associated virus serotype 8

<400> 15

atggctgccg atggttatct tccagattgg ctcgaggaca acctctctga gggcattcgc 60

gagtggtggg cgctgaaacc tggagccccg aagcccaaag ccaaccagca aaagcaggac 120

gacggccggg gtctggtgct tcctggctac aagtacctcg gacccttcaa cggactcgac 180

aagggggagc ccgtcaacgc ggcggacgca gcggccctcg agcacgacaa ggcctacgac 240

cagcagctgc aggcgggtga caatccgtac ctgcggtata accacgccga cgccgagttt 300

caggagcgtc tgcaagaaga tacgtctttt gggggcaacc tcgggcgagc agtcttccag 360

gccaagaagc gggttctcga acctctcggt ctggttgagg aaggcgctaa gacggctcct 420

ggaaagaaga gaccggtaga gccatcaccc cagcgttctc cagactcctc tacgggcatc 480

ggcaagaaag gccaacagcc cgccagaaaa agactcaatt ttggtcagac tggcgactca 540

gagtcagttc cagaccctca acctctcgga gaacctccag cagcgccctc tggtgtggga 600

cctaatacaa tggctgcagg cggtggcgca ccaatggcag acaataacga aggcgccgac 660

ggagtgggta gttcctcggg aaattggcat tgcgattcca catggctggg cgacagagtc 720

atcaccacca gcacccgaac ctgggccctg cccacctaca acaaccacct ctacaagcaa 780

atctccaacg ggacatcggg aggagccacc aacgacaaca cctacttcgg ctacagcacc 840

ccctgggggt attttgactt taacagattc cactgccact tttcaccacg tgactggcag 900

cgactcatca acaacaactg gggattccgg cccaagagac tcagcttcaa gctcttcaac 960

atccaggtca aggaggtcac gcagaatgaa ggcaccaaga ccatcgccaa taacctcacc 1020

agcaccatcc aggtgtttac ggactcggag taccagctgc cgtacgttct cggctctgcc 1080

caccagggct gcctgcctcc gttcccggcg gacgtgttca tgattcccca gtacggctac 1140

ctaacactca acaacggtag tcaggccgtg ggacgctcct ccttctactg cctggaatac 1200

tttccttcgc agatgctgag aaccggcaac aacttccagt ttacttacac cttcgaggac 1260

gtgcctttcc acagcagcta cgcccacagc cagagcttgg accggctgat gaatcctctg 1320

attgaccagt acctgtacta cttgtctcgg actcaaacaa caggaggcac ggcaaatacg 1380

cagactctgg gcttcagcca aggtgggcct aatacaatgg ccaatcaggc aaagaactgg 1440

ctgccaggac cctgttaccg ccaacaacgc gtctcaacga caaccgggca aaacaacaat 1500

agcaactttg cctggactgc tgggaccaaa taccatctga atggaagaaa ttcattggct 1560

aatcctggca tcgctatggc aacacacaaa gacgacgagg agcgtttttt tcccagtaac 1620

gggatcctga tttttggcaa acaaaatgct gccagagaca atgcggatta cagcgatgtc 1680

atgctcacca gcgaggaaga aatcaaaacc actaaccctg tggctacaga ggaatacggt 1740

atcgtggcag ataacttgca gcagcaaaac acggctcctc aaattggaac tgtcaacagc 1800

cagggggcct tacccggtat ggtctggcag aaccgggacg tgtacctgca gggtcccatc 1860

tgggccaaga ttcctcacac ggacggcaac ttccacccgt ctccgctgat gggcggcttt 1920

ggcctgaaac atcctccgcc tcagatcctg atcaagaaca cgcctgtacc tgcggatcct 1980

ccgaccacct tcaaccagtc aaagctgaac tctttcatca cgcaatacag caccggacag 2040

gtcagcgtgg aaattgaatg ggagctgcag aaggaaaaca gcaagcgctg gaaccccgag 2100

atccagtaca cctccaacta ctacaaatct acaagtgtgg actttgctgt taatacagaa 2160

ggcgtgtact ctgaaccccg ccccattggc acccgttacc tcacccgtaa tctgtaa 2217

<210> 16

<211> 2208

<212> DNA

<213> adeno-associated Virus, hu.13

<400> 16

atggctgccg atggttatct tccagattgg ctcgaggaca ctctctctga aggaataaga 60

cagtggtgga agctcaaacc tggcccacca ccaccaaagc ccgcagagcg gcataaggac 120

gacagcaggg gtcttgtgct tcctgggtac aagtacctcg gacccttcaa cggactcgac 180

aagggagagc cggtcaacga ggcagacgcc gcggccctcg agcacgacaa ggcctacgac 240

cggcagctcg acagcggaga caacccgtac ctcaagtaca accacgccga cgcggagttt 300

caggagcgcc ttaaagaaga tacgtctttt gggggcaacc tcggacgagc agtcttccag 360

gcaaaaaaga gggttcttga acctctgggc ctggttgagg agcctgttaa aacggctccg 420

ggaaaaaaga ggccggtaga gcactctcct gcggagccag actcctcctc gggaaccgga 480

aaagcgggcc agcagcctgc aagaaaaaga ttgaatttcg gtcagactgg agacgcagac 540

tccgtacctg acccccagcc tctcggacag ccaccagcag ccccctctgg tctgggaact 600

aatacgatgg cttcaggcag tggcgcacca atggcagaca ataacgaggg cgccgacgga 660

gtgggtaatt cctcgggaaa ttggcattgc gattccacat ggatgggcga cagagtcatc 720

accaccagca cccgaacttg ggccctgccc acctacaaca accatctcta caagcaaatc 780

tccagccaat caggagccag caacgacaac cactactttg gctacagcac cccttggggg 840

tattttgact tcaacagatt ccactgccac ttttcaccac gtgactggca aagactcatc 900

aacaacaact ggggattccg gcccaagaga ctcaacttca agctctttaa cattcaagtc 960

aaagaggtca cgcagaatga cggtacgacg acgattgcca ataaccttac cagcacggtt 1020

caggtgttta ctgactcgga gtaccagctc ccgtacgtcc tcggctcggc gcatcaagga 1080

tgcctcccgc cgttcccagc agacgtcttc atggtgccac agtatggata cctcaccctg 1140

aacaacggga gtcaggcagt aggacgctct tcattttact gcctggagta ctttccttct 1200

cagatgctgc gtaccggaaa caactttacc ttcagctaca cctttgagga cgttcctttc 1260

cacagcagct acgctcacag ccagagtttg gaccgtctca tgaatcctct catcgaccag 1320

tacctgtatt acttgagcag aacaaacact ccaagcggaa ccaccacgca gtccaggctt 1380

cagttttctc aggccggagc aagtgacatt cgggaccagt ctaggaactg gcttcctgga 1440

ccctgttacc gccagcagcg agtatcaaag acatctgcgg ataacaacaa cagtgaatac 1500

tcgtggactg gagctaccaa gtaccacctc aatggcagag actctctggt gaatccgggc 1560

ccggccatgg ccagccacaa ggacgatgaa gaaaagtttt ttcctcagag cggggttctc 1620

atctttggga agcaaggctc agagaaaaca aatgtggaca ttgaaaaggt catgattaca 1680

gacgaagagg aaatcaggac caccaatccc gtggctacgg agcagtatgg ttctgtatct 1740

accaacctgc agggcggcaa cacacaagca gctaccgcag atgtcaacac acaaggcgtt 1800

cttccaggca tggtctggca ggacagagac gtgtacctgc aggggcccat ctgggcaaag 1860

attccacaca cggacggaca ttttcacccc tctcccctca tgggcggatt cggacttaaa 1920

caccctcctc cacagattct catcaagaac accccggtac ctgcgaatcc ttcgaccacc 1980

ttcagtgcgg caaagtttgc ttctttcatc acacagtatt ccacggggca ggtcagcgtg 2040

gagatcgagt gggagctgca gaaggagaac agcaaacgct ggaatcccga gatccagtac 2100

acttccaact acaacaaatc tgttaatgtg gactttactg ttgacactaa tggcgtgtat 2160

tcagagcctc gccccattgg caccagatac ctgactcgta atctgtaa 2208

<210> 17

<211> 2208

<212> DNA

<213> adeno-associated Virus, hu.26

<400> 17

atggctgccg atggttatct tccagattgg ctcgaggaca ctctctctga aggaataaga 60

cagtggtgga agctcaaacc tggcccacca ccaccaaagc ccgcagagcg gcataaggac 120

gacagcaggg gtcttgtgct tcctgggtac aagtacctcg gacccttcaa cggactcgac 180

aagggagagc cggtcaacga ggcagacgcc gcggccctcg agcacgacaa ggcctacgac 240

cggcagctcg acagcggaga caacccgtac ctcaagtaca accacgccga cgcggagttt 300

caggagcgtc ttaaagaaga tacgtctttt gggggcaacc tcggacgagc agtcttccag 360

gccaaaaaga ggattcttga acctctgggc ctggttgagg aacctgttaa gacggctccg 420

ggaaaaaaga ggccggtaga gcactctcct gcggagccag actcctcctc gggaaccgga 480

aaagcgggcc agcagcctgc aagaaagaga ttgaattttg gtcagactgg agacgcagac 540

tcagtacctg acccccagcc tctcggacag ccaccagcag ccccctctgg tctgggaact 600

aatacgatgg cttcaggcag tggcgcacca atggcagaca ataacgaggg cgccgacgga 660

gtgggtaatt cctcgggaaa ttggcattgc gattccacat ggatgggcga cagagtcatc 720

accaccagca cccgcacctg ggccctgccc acctacaaca accatctgta caagcaaatc 780

tccagccagt ctggagccag caacgacaac cactactttg gctacagcac cccctggggg 840

tattttgact tcaacagatt ccactgccac ttctccccac gtgactggca aagactcatc 900

aacaacaact ggggattccg gcccaagaga ctcagcttca agctctttaa cattcaagtc 960

aaagaggtca cgcagaatga cggtacgacg acgattgcca ataaccttac cagcacggtt 1020

caggtgttta ctgactcgga gtaccagctc ccgtacgtcc tcggctcggc gcatcaagga 1080

tgcctcccgc cgttcccagc agacgtcttc atggtgccac agtatggata cctcaccctg 1140

aacaacggca gtcaggcggt aggacgctct tccttttact gcctggagta ctttccttct 1200

cagatgcttc gtaccggaaa caactttacc ttcagctaca cctttgaaga cgttcctttc 1260

catagcagct acgctcacag ccaaagtctg gaccgtctca tgaatcctct catcgaccag 1320

tacctgtatt acttgagcag aacaaacact ccaagcggaa ccaccacgat gtccaggctt 1380

cagttttctc aggccggagc aagtgacatt cgggaccagt ctagaaactg gcttcctgga 1440

ccctgttacc gccagcagcg agtatcaaag acagctgcgg acaacaacaa cagtgattac 1500

tcgtggactg gagctaccaa gtaccacctc aatggaagag actctctggt gaatccgggc 1560

ccagctatgg ccagccacaa ggacgatgaa gaaaaatatt ttcctcagag cggggttctc 1620

atctttggaa aacaagactc gggaaaaact aatgtggaca ttgaaaaggt tatgattaca 1680

gacgaagagg aaatcaggac caccaatccc gtggctacgg agcagtatgg ttctgtatct 1740

accaacctcc agagcggcaa cacacaagca gctacctcag atgtcaacac acaaggcgtt 1800

cttccaggca tggtctggca ggacagagac gtgtacctgc aggggcccat ctgggcaaag 1860

attccacaca cggacggaca ttttcacccc tctcccctca tgggcggatt cggacttaaa 1920

caccctcctc cacaaattct catcaagaac accccggtac ctgcgaatcc ttcgaccact 1980

ttcagtgcgg caaagtttgc ttccttcatc acacagtact ccacggggca ggtcagcgtg 2040

gagatcgagt gggagctgca gaaggagaac agcaaacgct ggaatcccga aattcagtac 2100

acttccaact acaacaaatc tgttaatgtg gactttactg tggacactaa tggtgtgtat 2160

tcagagcctc gccccattgg caccagatac ctgactcgta atctgtaa 2208

<210> 18

<211> 2217

<212> DNA

<213> adeno-associated Virus, hu.37

<400> 18

atggctgctg acggttatct tccagattgg ctcgaggaca acctctctga gggcattcgc 60

gagtggtggg acctgaaacc tggagccccc aagcccaagg ccaaccagca gaagcaggac 120

gacggccggg gtctggtgct tcctggctac aagtacctcg gacccttcaa cggactcgac 180

aagggggagc ccgtcaacgc ggcggacgca gcggccctcg agcacgacaa ggcctacgac 240

cagcagctca aagcgggtga caatccgtac ctgcggtata accacgccga cgccgagttt 300

caggagcgtc tgcaagaaga tacgtctttt gggggcaacc tcgggcgagc agtcttccag 360

gccaagaagc gggttctcga acctctcggt ctggttgagg aagctgctaa gacggctcct 420

ggaaagaaga gaccggtaga accgtcacct cagcgttccc ccgactcctc cacgggcatc 480

ggcaagaaag gccagcagcc cgctaaaaag agactgaact ttggtcagac tggcgactca 540

gagtcagtcc ccgaccctca accaatcgga gaaccaccag caggcccctc tggtctggga 600

tctggtacaa tggctgcagg cggtggcgct ccaatggcag acaataacga aggcgccgac 660

ggagtgggta gttcctcagg aaattggcat tgcgattcca catggctggg cgacagagtc 720

atcaccacca gcacccgaac ctgggccctg cccacctaca acaaccacct ctacaagcaa 780

atatccaatg ggacatcggg aggaagcacc aacgacaaca cctacttcgg ctacagcacc 840

ccctgggggt attttgactt caacagattc cactgccact tctcaccacg tgactggcag 900

cgactcatca acaacaactg gggattccgg ccaaaaagac tcagcttcaa gctcttcaac 960

atccaggtca aggaggtcac gcagaatgaa ggcaccaaga ccatcgccaa taaccttacc 1020

agcacgattc aggtatttac ggactcggaa taccagctgc cgtacgtcct cggctccgcg 1080

caccagggct gcctgcctcc gttcccggcg gacgtcttca tgattcccca gtacggctac 1140

cttacactga acaatggaag tcaagccgta ggccgttcct ccttctactg cctggaatat 1200

tttccatctc aaatgctgcg aactggaaac aattttgaat tcagctacac cttcgaggac 1260

gtgcctttcc acagcagcta cgcacacagc cagagcttgg accgactgat gaatcctctc 1320

atcgaccagt acctgtacta cttatccaga actcagtcca caggaggaac tcaaggtacc 1380

cagcaattgt tattttctca agctgggcct gcaaacatgt cggctcaggc taagaactgg 1440

ctacctggac cttgctaccg gcagcagcga gtctctacga cactgtcgca aaacaacaac 1500

agcaactttg cttggactgg tgccaccaaa tatcacctga acggaagaga ctctttggta 1560

aatcccggtg tcgccatggc aacccacaag gacgacgagg aacgcttctt cccgtcgagt 1620

ggagtcctga tgttcggaaa acagggtgct ggaagagaca atgtggacta cagcagcgtt 1680

atgctaacca gcgaagaaga aattaaaacc actaaccccg tagccacaga acaatacggt 1740

gtggtggctg acaacttgca gcaaaccaat acagggccta ttgtgggaaa tgtcaacagc 1800

caaggagcct tacctggcat ggtctggcag aaccgagacg tgtacctgca gggtcccatc 1860

tgggccaaga ttcctcacac ggacggcaac ttccaccctt caccgctaat gggaggattt 1920

ggactgaagc acccacctcc tcagatcctg atcaagaaca cgccggtacc tgcggatcct 1980

ccaacaacgt tcagccaggc gaaattggct tccttcatta cgcagtacag caccggacag 2040

gtcagcgtgg aaatcgagtg ggagctgcag aaggagaaca gcaaacgctg gaacccagag 2100

attcagtaca cttcaaacta ctacaaatct acaaatgtgg actttgctgt caatacagag 2160

ggaacttatt ctgagcctcg ccccattggt actcgttacc tcacccgtaa tctgtaa 2217

<210> 19

<211> 2205

<212> DNA

<213> adeno-associated Virus, hu.53

<400> 19

atggctgccg atggttatct tccagattgg ctcgaggaca ctctctctga aggaataaga 60

cagtggtgga agctcaaacc tggcccacca ccaccaaagc ccgcagagcg gcataaggac 120

gacagcaggg gtcttgtgct tcctgggtac aagtacctcg gacccttcaa cggactcgac 180

aagggagagc cggtcaacga ggcagacgcc gcggccctcg agcacgacaa ggcctacgac 240

cggcagctcg acagcggaga caacccgtac ctcaagtaca accacgccga cgcggagttt 300

caggagcgtc ttaaagaaga tacgtctttt gggggcaacc tcggacgagc agtcttccag 360

gcgaaaaaga gggttcttga acctctgggc ctggttgagg aacctgttaa gacggctccg 420

ggaaaaaaga ggccggtaga gcactctcct gcggagccag actcctcctc gggaaccgga 480

aaagcgggcc agcagcctgc aagaaaaaga ctgaatttcg gtcagactgg agacgcagac 540

tccgtacctg acccccagcc tctcagacag ccaccagcag cccccacaag tttgggatct 600

actacaatgg ctacaggcag tggcgcacca atggcagaca ataacgaggg tgccgatgga 660

gtgggtaatt cctcaggaaa ttggcattgc gattcccaat ggctgggcga cagagtcatc 720

accaccagca cccgaacctg ggccctgccc acctacaaca accaccttta caagcaaatc 780

tccagccaat caggagcctc aaacgacaac cactactttg gctacagcac cccctggggg 840

tattttgact tcaacagatt ccactgccac ttttcaccac gtgactggca aagactcatc 900

aacaacaact ggggattccg acccaagaga ctcaacttca agctctttaa cattcaagtc 960

aaagaggtca cgcagaatga cggtacgacg acgattgcca ataaccttac cagcacggtt 1020

caggtgttta ctgactcgga gtaccagctc ccgtacgtcc tcggctcggc gcatcaagga 1080

tgcctcccgc cgtttccagc ggacgtcttc atggtcccac agtatggata cctcaccctg 1140

aacaacggga gtcaggcggt aggacgctct tccttttact gcctggagta ctttccttct 1200

cagatgctgc gtactggaaa caactttcag ttcagctaca cttttgaaga cgtgcctttc 1260

cacagcagct acgctcacag ccagagtttg gatcggctga tgaatcctct gatcgaccag 1320

tacctgtatt atctaaacag aacacaaaca gctagtggaa ctcagcagtc tcggctactg 1380

tttagccaag ctggacccac aagcatgtct cttcaagcta aaaactggct gcctggaccg 1440

tgttatcgcc agcagcgttt gtcaaagcag gcaaacgaca acaacaacag caactttccc 1500

tggactggag ctaccaagta ctacctcaat ggcagagact ctttggtgaa cccgggcccg 1560

gccatggcca gccacaagga cgatgaagaa aagtttttcc ccatgcatgg aaccctaata 1620

tttggtaaag aaggaacaaa tgctaccaac gcggaattgg aaaatgtcat gattacagat 1680

gaagaggaaa tcaggaccac caatcccgtg gctacagagc agtacggata tgtgtcaaat 1740

aatttgcaaa actcaaatac tgctgcaagt actgaaactg tgaatcacca aggagcatta 1800

cctggtatgg tgtggcagga tcgagacgtg tacctgcagg gacccatttg ggccaagatt 1860

cctcacaccg atggacactt tcatccttct ccactgatgg gaggttttgg actcaaacac 1920

ccgcctcctc agattatgat caaaaacact cccgttccag ccaatcctcc cacaaacttc 1980

agttctgcca agtttgcttc cttcatcaca cagtattcca cgggacaggt cagcgtggag 2040

atcgagtggg agctgcagaa ggagaacagc aaacgctgga atcccgaaat tcagtacact 2100

tccaactaca acaaatctgt taatgtggac tttactgtgg acactaatgg tgtgtattca 2160

gagcctcgcc ccattggcac cagatacctg actcgtaatc tgtaa 2205

<210> 20

<211> 2217

<212> DNA

<213> macaque gland-associated Virus, rh.39

<400> 20

atggctgctg acggttatct tccagattgg ctcgaggaca acctctctga gggcattcgc 60

gagtggtggg acctgaaacc tggagccccc aagcccaagg ccaaccagca gaagcaggac 120

gacggccggg gtctggtgct tcctggctac aagtacctcg gacccttcaa cggactcgac 180

aagggggagc ccgtcaacgc ggcggacgca gcggccctcg agcacgacaa ggcctacgac 240

cagcagctca aagcgggtga caatccgtac ctgcggtata accacgccga cgccgagttt 300

caggagcgtc tgcaagaaga tacgtctttt gggggcaacc tcgggcgagc agtcttccag 360

gccaagaagc gggttctcga acctctcggt ctggttgagg aagctgctaa gacggctcct 420

ggaaagaaga gaccggtaga accgtcacct cagcgttccc ccgactcctc cacgggcatc 480

ggcaagaaag gccagcagcc cgctaaaaag agactgaact ttggtcagac tggcgactca 540

gagtcagtcc ccgaccctca accaatcgga gaaccaccag caggcccctc tggtctggga 600

tctggtacaa tggctgcagg cggtggcgct ccaatggcag acaataacga aggcgccgac 660

ggagtgggta gttcctcagg aaattggcat tgcgattcca catggctggg cgacagagtc 720

atcaccacca gcacccgaac ctgggccctg cccacctaca acaaccacct ctacaagcaa 780

atatccaatg ggacatcggg aggaagcacc aacgacaaca cctacttcgg ctacagcacc 840

ccctgggggt attttgactt caacagattc cactgccact tctcaccacg tgactggcag 900

cgactcatca acaacaactg gggattccgg ccaaaaagac tcagcttcaa gctcttcaac 960

atccaggtca aggaggtcac gcagaatgaa ggcaccaaga ccatcgccaa taaccttacc 1020

agcacgattc aggtatttac ggactcggaa taccagctgc cgtacgtcct cggctccgcg 1080

caccagggct gcctgcctcc gttcccggcg gacgtcttca tgattcccca gtacggctac 1140

cttacactga acaatggaag tcaagccgta ggccgttcct ccttctactg cctggaatat 1200

tttccatctc aaatgctgcg aactggaaac aattttgaat tcagctacac cttcgaggac 1260

gtgcctttcc acagcagcta cgcacacagc cagagcttgg accgactgat gaatcctctc 1320

atcgaccagt acctgtacta cttatccaga actcagtcca caggaggaac tcaaggtacc 1380

cagcaattgt tattttctca agctgggcct gcaaacatgt cggctcaggc taagaactgg 1440

ctacctggac cttgctaccg gcagcagcga gtctctacga cactgtcgca aaacaacaac 1500

agcaactttg cttggactgg tgccaccaaa tatcacctga acggaagaga ctctttggta 1560

aatcccggtg tcgccatggc aacccacaag gacgacgagg aacgcttctt cccgtcgagt 1620

ggagtcctga tgtttggaaa acagggtgct ggaagagaca atgtggacta cagcagcgtt 1680

atgctaacca gcgaagaaga aattaaaacc actaaccctg tagccacaga acaatacggt 1740

gtggtggctg ataacttgca gcaaaccaat acggggccta ttgtgggaaa tgtcaacagc 1800

caaggagcct tacctggcat ggtctggcag aaccgagacg tgtacctgca gggtcccatc 1860

tgggccaaga ttcctcacac ggacggcaac ttccaccctt caccgctaat gggaggattt 1920

ggactgaagc acccacctcc tcagatcctg atcaagaaca cgccggtacc tgcggatcct 1980

ccaacaacgt tcagccaggc gaaattggct tccttcatta cgcagtacag caccggacag 2040

gtcagcgtgg aaatcgagtg ggagctgcag aaggagaaca gcaaacgctg gaacccagag 2100

attcagtaca cttcaaacta ctacaaatct acaaatgtgg actttgctgt caatacagag 2160

ggaacttatt ctgagcctcg ccccattggt actcgttacc tcacccgtaa tctgtaa 2217

<210> 21

<211> 2211

<212> DNA

<213> macaque gland-associated Virus, rh.43

<400> 21

atggctgccg atggttatct tccagattgg ctcgaggaca acctctctga gggcattcgc 60

gagtggtggg acttgaaacc tggagccccg aaacccaaag ccaaccagca aaagcaggac 120

gacggccggg gcctggtgct tcctggctac aagtacctcg gacccttcaa cggactcgac 180

aagggggagc ccgtcaacgc ggcggacgca gcggccctcg agcacgacaa ggcctacgac 240

cagcagctcg aagcgggtga caatccgtac ctgcggtata accacgccga cgccgagttt 300

caggagcgtc tgcaagaaga tacgtctttt gggggcaacc tcgggcgagc agtcttccag 360

gccaagaagc gggttctcga acctctcggt ctggttgagg aaggcgctaa gacggctcct 420

ggaaagaaga gaccagtaga gcagtcaccc caagaaccag actcctcctc gggcatcggc 480

aagaaaggcc aacagcccgc cagaaaaaga ctcaattttg gccagactgg cgactcagag 540

tcagttccag accctcaacc tctcggagaa cctccagcag cgccctctgg tgtgggacct 600

aatacaatgg ctgcaggcgg tggcgcacca atggcagaca ataacgaagg cgccgacgga 660

gtgggtagtt cctcgggaaa ttggcattgc gattccacat ggctgggcga cagagtcatc 720

accaccagca cccgaacctg ggccctgccc acctacaaca accacctcta caagcaaatc 780

tccaacggga catcgggagg agccaccaac gacaacacct acttcggcta cagcaccccc 840

tgggggtatt ttgactttaa cagattccac tgccactttt caccacgtga ctggcagcga 900

ctcatcaaca acaactgggg attccggccc aagagactca gcttcaagct cttcaacatc 960

caggtcaagg aggtcacgca gaatgaaggc accaagacca tcgccaataa cctcaccagc 1020

accatccagg tgtttacgga ctcggagtac cagctgccgt acgttctcgg ctctgcccac 1080

cagggctgcc tgcctccgtt cccggcggac gtgttcatga ttccccagta cggctaccta 1140

acactcaaca acggtagtca ggccgtggga cgctcctcct tctactgcct ggaatacttt 1200

ccttcgcaga tgctgagaac cggcaacaac ttccagttta cttacacctt cgaggacgtg 1260

cctttccaca gcagctacgc ccacagccag agcttggacc ggctgatgaa tcctctgatt 1320

gaccagtacc tgtactactt gtctcggact caaacaacag gaggcacggc aaatacgcag 1380

actctgggct tcagccaagg tgggcctaat acaatggcca atcaggcaaa gaactggctg 1440

ccaggaccct gttaccgcca acaacgcgtc tcaacgacaa ccgggcaaaa caacaatagc 1500

aactttgcct ggactgctgg gaccaaatac catctgaatg gaagaaattc attggctaat 1560

cctggcatcg ctatggcaac acacaaagac gacgaggagc gttttttccc agtaacggga 1620

tcctgttttt ggcaacaaaa tgctgccaga gacaatgcgg attacagcga tgtcatgctc 1680

accagcgagg aagaaatcaa aaccactaac cctgtggcta cagaggaata cggtatcgtg 1740

gcagataact tgcagcagca aaacacggct cctcaaattg gaactgtcaa cagccagggg 1800

gccttacccg gtatggtctg gcagaaccgg gacgtgtacc tgcagggtcc catctgggcc 1860

aagattcctc acacggacgg caacttccac ccgtctccgc tgatgggcgg ctttggcctg 1920

aaacatcctc cgcctcagat cctgatcaag aacacgcctg tacctgcgga tcctccgacc 1980

accttcaacc agtcaaagct gaactctttc atcacgcaat acagcaccgg acaggtcagc 2040

gtggaaattg aatgggagct acagaaggaa aacagcaagc gctggaaccc cgagatccag 2100

tacacctcca actactacaa atctacaagt gtggactttg ctgttaatac agaaggcgtg 2160

tactctgaac cccgccccat tggcacccgt tacctcaccc gtaatctgta a 2211

<210> 22

<211> 2217

<212> DNA

<213> Actinidia adeno-associated virus, rh.46

<400> 22

atggctgccg atggttatct tccagattgg ctcgaggaca acctctctga gggcattcgc 60

gagtggtggg acctgaaacc tggagccccg aaacccaaag ccaaccagca aaagcaggac 120

gacggccggg gtctggtgct tcctggctac aagtacctcg gacccttcaa cggactcgac 180

aagggggagc ccgtcaacgc ggcggacgca gcggccctcg agcacgacaa ggcctacgac 240

cagcagctca aagcgggtga caatccgtac ctgcggtata atcacgccga cgccgagttt 300

caggagcgtc tgcaagaaga tacgtctttt gggggcaacc tcgggcgagc agtcttccag 360

gccaagaagc gggttctcga acctctcggt ctggttgagg aaggcgctaa gacggctcct 420

ggaaagaaga gaccggtaga gccgtcacca cagcgttccc ccgactcctc cacgggcatc 480

ggcaagaaag gccagcagcc cgccagaaag agactcaatt tcggtcagac tggcgactca 540

gagtcagtcc ccgaccctca acctatcgga gaacctccag cagcgccctc tagtgtggga 600

tctggtacaa tggctgcagg cggtggcgca ccaatggcag acaataacga aggtgccgac 660

ggagtgggta gttcctcggg aaattggcat tgcgattcca catggctggg cgacagagtc 720

atcaccacca gcacccgaac ctgggccctg cccacctaca acaaccacct ctacaagcaa 780

atctccaacg ggacctcggg aggcagcacc aacgacaaca cctactttgg ctacagcacc 840

ccctgggggt attttgactt taacagattc cactgccact tctcaccacg tgactggcag 900

cgactcatca acaacaactg gggattccgg cccaagagac tcagcttcaa gctcttcaac 960

atccaggtca aagaggtcac gcagaatgaa ggcaccaaga ccatcgccaa taacctcacc 1020

agcaccatcc aggtgtttac ggactcggaa taccagctgc cgtacgtcct cggctctgcc 1080

caccagggct gcctgcctcc gttcccggcg gacgtcttca tgattcctca gtacggctac 1140

ctgactctca acaacggtag tcaggccgtg ggacgttcct ccttctactg cctggagtac 1200

ttcccctctc agatgctgag aacgggcaac aacttttcct tcagctacac tttcgaggac 1260

gtgcctttcc acagcagcta cgcgcacagc cagagtttgg acaggctgat gaatcctctc 1320

atcgaccagt acctgtacta cctgtcaaga acccagtcta cgggaggcac agcgggaacc 1380

cagcagttgc tgttttctca ggccgggcct agcaacatgt cggctcaggc cagaaactgg 1440

ctgcctggac cctgctacag acagcagcgc gtctccacga cactgtcgca aaacaacaac 1500

agcaactttg cctggactgg tgccaccaag tatcatctga acggcagaga ctctctggtg 1560

aatccgggcg tcgccatggc aaccaacaag gacgacgagg accgcttctt cccatccagc 1620

ggcatcctca tgtttggcaa gcagggagct ggaaaagaca acgtggacta tagcaacgtg 1680

atgctaacca gcgaggaaga aatcaaggcc accaaccccg tggccacaga acagtatggc 1740

gtggtggctg ataacctaca gcagcaaaac accgctccta ttgtgggggc cgtcaacagc 1800

cagggagcct tacctggcat ggtctggcag aaccgggacg tgtacctgca gggtcctatt 1860

tgggccaaga ttcctcacac agatggcaac tttcacccgt ctcctttaat gggcggcttt 1920

ggacttaaac atccgcctcc tcagatcctc atcaaaaaca ctcctgttcc tgcggatcct 1980

ccaacagcgt tcaaccaggc caagctgaat tctttcatca cgcagtacag caccggacaa 2040

gtcagcgtgg agatcgagtg ggagctgcag aaggagaaca gcaagcgctg gaacccagag 2100

attcagtata cttccaacta ctacaaatct acaaatgtgg actttgctgt taatactgag 2160

ggtgtttact ctgagcctcg ccccattggc actcgttacc tcacccgtaa tctgtaa 2217

<210> 23

<211> 735

<212> PRT

<213> capsid protein of adeno-associated virus serotype 2

<400> 23

Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Thr Leu Ser

1 5 10 15

Glu Gly Ile Arg Gln Trp Trp Lys Leu Lys Pro Gly Pro Pro Pro Pro

20 25 30

Lys Pro Ala Glu Arg His Lys Asp Asp Ser Arg Gly Leu Val Leu Pro

35 40 45

Gly Tyr Lys Tyr Leu Gly Pro Phe Asn Gly Leu Asp Lys Gly Glu Pro

50 55 60

Val Asn Glu Ala Asp Ala Ala Ala Leu Glu His Asp Lys Ala Tyr Asp

65 70 75 80

Arg Gln Leu Asp Ser Gly Asp Asn Pro Tyr Leu Lys Tyr Asn His Ala

85 90 95

Asp Ala Glu Phe Gln Glu Arg Leu Lys Glu Asp Thr Ser Phe Gly Gly

100 105 110

Asn Leu Gly Arg Ala Val Phe Gln Ala Lys Lys Arg Val Leu Glu Pro

115 120 125

Leu Gly Leu Val Glu Glu Pro Val Lys Thr Ala Pro Gly Lys Lys Arg

130 135 140

Pro Val Glu His Ser Pro Val Glu Pro Asp Ser Ser Ser Gly Thr Gly

145 150 155 160

Lys Ala Gly Gln Gln Pro Ala Arg Lys Arg Leu Asn Phe Gly Gln Thr

165 170 175

Gly Asp Ala Asp Ser Val Pro Asp Pro Gln Pro Leu Gly Gln Pro Pro

180 185 190

Ala Ala Pro Ser Gly Leu Gly Thr Asn Thr Met Ala Thr Gly Ser Gly

195 200 205

Ala Pro Met Ala Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Asn Ser

210 215 220

Ser Gly Asn Trp His Cys Asp Ser Thr Trp Met Gly Asp Arg Val Ile

225 230 235 240

Thr Thr Ser Thr Arg Thr Trp Ala Leu Pro Thr Tyr Asn Asn His Leu

245 250 255

Tyr Lys Gln Ile Ser Ser Gln Ser Gly Ala Ser Asn Asp Asn His Tyr

260 265 270

Phe Gly Tyr Ser Thr Pro Trp Gly Tyr Phe Asp Phe Asn Arg Phe His

275 280 285

Cys His Phe Ser Pro Arg Asp Trp Gln Arg Leu Ile Asn Asn Asn Trp

290 295 300

Gly Phe Arg Pro Lys Arg Leu Asn Phe Lys Leu Phe Asn Ile Gln Val

305 310 315 320

Lys Glu Val Thr Gln Asn Asp Gly Thr Thr Thr Ile Ala Asn Asn Leu

325 330 335

Thr Ser Thr Val Gln Val Phe Thr Asp Ser Glu Tyr Gln Leu Pro Tyr

340 345 350

Val Leu Gly Ser Ala His Gln Gly Cys Leu Pro Pro Phe Pro Ala Asp

355 360 365

Val Phe Met Val Pro Gln Tyr Gly Tyr Leu Thr Leu Asn Asn Gly Ser

370 375 380

Gln Ala Val Gly Arg Ser Ser Phe Tyr Cys Leu Glu Tyr Phe Pro Ser

385 390 395 400

Gln Met Leu Arg Thr Gly Asn Asn Phe Thr Phe Ser Tyr Thr Phe Glu

405 410 415

Asp Val Pro Phe His Ser Ser Tyr Ala His Ser Gln Ser Leu Asp Arg

420 425 430

Leu Met Asn Pro Leu Ile Asp Gln Tyr Leu Tyr Tyr Leu Ser Arg Thr

435 440 445

Asn Thr Pro Ser Gly Thr Thr Thr Gln Ser Arg Leu Gln Phe Ser Gln

450 455 460

Ala Gly Ala Ser Asp Ile Arg Asp Gln Ser Arg Asn Trp Leu Pro Gly

465 470 475 480

Pro Cys Tyr Arg Gln Gln Arg Val Ser Lys Thr Ser Ala Asp Asn Asn

485 490 495

Asn Ser Glu Tyr Ser Trp Thr Gly Ala Thr Lys Tyr His Leu Asn Gly

500 505 510

Arg Asp Ser Leu Val Asn Pro Gly Pro Ala Met Ala Ser His Lys Asp

515 520 525

Asp Glu Glu Lys Phe Phe Pro Gln Ser Gly Val Leu Ile Phe Gly Lys

530 535 540

Gln Gly Ser Glu Lys Thr Asn Val Asp Ile Glu Lys Val Met Ile Thr

545 550 555 560

Asp Glu Glu Glu Ile Arg Thr Thr Asn Pro Val Ala Thr Glu Gln Tyr

565 570 575

Gly Ser Val Ser Thr Asn Leu Gln Arg Gly Asn Arg Gln Ala Ala Thr

580 585 590

Ala Asp Val Asn Thr Gln Gly Val Leu Pro Gly Met Val Trp Gln Asp

595 600 605

Arg Asp Val Tyr Leu Gln Gly Pro Ile Trp Ala Lys Ile Pro His Thr

610 615 620

Asp Gly His Phe His Pro Ser Pro Leu Met Gly Gly Phe Gly Leu Lys

625 630 635 640

His Pro Pro Pro Gln Ile Leu Ile Lys Asn Thr Pro Val Pro Ala Asn

645 650 655

Pro Ser Thr Thr Phe Ser Ala Ala Lys Phe Ala Ser Phe Ile Thr Gln

660 665 670

Tyr Ser Thr Gly Gln Val Ser Val Glu Ile Glu Trp Glu Leu Gln Lys

675 680 685

Glu Asn Ser Lys Arg Trp Asn Pro Glu Ile Gln Tyr Thr Ser Asn Tyr

690 695 700

Asn Lys Ser Val Asn Val Asp Phe Thr Val Asp Thr Asn Gly Val Tyr

705 710 715 720

Ser Glu Pro Arg Pro Ile Gly Thr Arg Tyr Leu Thr Arg Asn Leu

725 730 735

<210> 24

<211> 728

<212> PRT

<213> cy.5 capsid protein

<400> 24

Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Gly Asn Leu Ser

1 5 10 15

Glu Gly Ile Arg Glu Trp Trp Asp Leu Lys Pro Gly Ala Pro Lys Pro

20 25 30

Lys Ala Asn Gln Gln Lys Gln Asp Asp Gly Arg Gly Leu Val Leu Pro

35 40 45

Gly Tyr Arg Tyr Leu Gly Pro Phe Asn Gly Leu Asp Lys Gly Glu Pro

50 55 60

Val Asn Glu Ala Asp Ala Ala Ala Leu Glu His Asp Lys Ala Tyr Asp

65 70 75 80

Lys Gln Leu Glu Gln Gly Asp Asn Pro Tyr Leu Lys Tyr Asn His Ala

85 90 95

Asp Ala Glu Phe Gln Glu Arg Leu Gln Glu Asp Thr Ser Phe Gly Gly

100 105 110

Asn Leu Gly Arg Ala Val Phe Gln Ala Lys Lys Arg Val Leu Glu Pro

115 120 125

Leu Gly Leu Val Glu Glu Gly Ala Lys Thr Ala Pro Gly Lys Lys Arg

130 135 140

Pro Ile Glu Ser Pro Asp Ser Ser Thr Gly Ile Gly Lys Asn Gly Gln

145 150 155 160

Pro Pro Ala Lys Lys Lys Leu Asn Phe Gly Gln Thr Gly Asp Ser Glu

165 170 175

Ser Val Pro Asp Pro Gln Pro Leu Gly Glu Pro Pro Ala Ala Pro Ser

180 185 190

Gly Leu Gly Ser Gly Thr Met Ala Ala Gly Gly Gly Ala Pro Met Ala

195 200 205

Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Asn Ala Ser Gly Asn Trp

210 215 220

His Cys Asp Ser Thr Trp Leu Gly Asp Arg Val Ile Thr Thr Ser Thr

225 230 235 240

Arg Thr Trp Ala Leu Pro Thr Tyr Asn Asn His Leu Tyr Lys Gln Ile

245 250 255

Ser Ser Gln Ser Gly Ala Thr Asn Asp Asn His Phe Phe Gly Tyr Ser

260 265 270

Thr Pro Trp Gly Tyr Phe Asp Phe Asn Arg Phe His Cys His Phe Ser

275 280 285

Pro Arg Asp Trp Gln Arg Leu Ile Asn Asn Asn Trp Gly Phe Arg Pro

290 295 300

Arg Lys Leu Arg Phe Lys Leu Phe Asn Ile Gln Val Lys Glu Val Thr

305 310 315 320

Thr Asn Asp Gly Val Thr Thr Ile Ala Asn Asn Leu Thr Ser Thr Ile

325 330 335

Gln Val Phe Ser Asp Ser Glu Tyr Gln Leu Pro Tyr Val Leu Gly Ser

340 345 350

Ala His Gln Gly Cys Leu Pro Pro Phe Pro Ala Asp Val Phe Met Ile

355 360 365

Pro Gln Tyr Gly Tyr Leu Thr Leu Asn Asn Gly Ser Gln Ser Val Gly

370 375 380

Arg Ser Ser Phe Tyr Cys Leu Glu Tyr Phe Pro Ser Gln Met Leu Arg

385 390 395 400

Thr Gly Asp Asn Phe Glu Phe Ser Tyr Thr Phe Glu Glu Val Pro Phe

405 410 415

His Ser Ser Tyr Ala His Ser Gln Ser Leu Asp Arg Leu Met Asn Pro

420 425 430

Leu Ile Asp Gln Tyr Leu Tyr Tyr Leu Ala Arg Thr Gln Ser Thr Thr

435 440 445

Gly Ser Thr Arg Glu Leu Gln Phe His Gln Ala Gly Pro Asn Thr Met

450 455 460

Ala Glu Gln Ser Lys Asn Trp Leu Pro Gly Pro Cys Tyr Arg Gln Gln

465 470 475 480

Arg Leu Ser Lys Asn Ile Asp Ser Asn Asn Asn Ser Asn Phe Ala Trp

485 490 495

Thr Gly Ala Thr Lys Tyr His Leu Asn Gly Arg Asn Ser Leu Thr Asn

500 505 510

Pro Gly Val Ala Met Ala Thr Asn Lys Asp Asp Glu Asp Gln Phe Phe

515 520 525

Pro Ile Asn Gly Val Leu Val Phe Gly Lys Thr Gly Ala Ala Asn Lys

530 535 540

Thr Thr Leu Glu Asn Val Leu Met Thr Ser Glu Glu Glu Ile Lys Thr

545 550 555 560

Thr Asn Pro Val Ala Thr Glu Glu Tyr Gly Val Val Ser Ser Asn Leu

565 570 575

Gln Ser Ser Thr Ala Gly Pro Gln Thr Gln Thr Val Asn Ser Gln Gly

580 585 590

Ala Leu Pro Gly Met Val Trp Gln Asn Arg Asp Val Tyr Leu Gln Gly

595 600 605

Pro Ile Trp Ala Lys Ile Pro His Thr Asp Gly Asn Phe His Pro Ser

610 615 620

Pro Leu Met Gly Gly Phe Gly Leu Lys His Pro Pro Pro Gln Ile Leu

625 630 635 640

Ile Lys Asn Thr Pro Val Pro Ala Asn Pro Pro Glu Val Phe Thr Pro

645 650 655

Ala Lys Phe Ala Ser Phe Ile Thr Gln Tyr Ser Thr Gly Gln Val Ser

660 665 670

Val Glu Ile Glu Trp Glu Leu Gln Lys Glu Asn Ser Lys Arg Trp Asn

675 680 685

Pro Glu Ile Gln Tyr Thr Ser Asn Tyr Ala Lys Ser Asn Asn Val Glu

690 695 700

Phe Ala Val Asn Asn Glu Gly Val Tyr Thr Glu Pro Arg Pro Ile Gly

705 710 715 720

Thr Arg Tyr Leu Thr Arg Asn Leu

725

<210> 25

<211> 738

<212> PRT

<213> capsid protein of macaque gland-associated virus, rh.10

<400> 25

Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser

1 5 10 15

Glu Gly Ile Arg Glu Trp Trp Asp Leu Lys Pro Gly Ala Pro Lys Pro

20 25 30

Lys Ala Asn Gln Gln Lys Gln Asp Asp Gly Arg Gly Leu Val Leu Pro

35 40 45

Gly Tyr Lys Tyr Leu Gly Pro Phe Asn Gly Leu Asp Lys Gly Glu Pro

50 55 60

Val Asn Ala Ala Asp Ala Ala Ala Leu Glu His Asp Lys Ala Tyr Asp

65 70 75 80

Gln Gln Leu Lys Ala Gly Asp Asn Pro Tyr Leu Arg Tyr Asn His Ala

85 90 95

Asp Ala Glu Phe Gln Glu Arg Leu Gln Glu Asp Thr Ser Phe Gly Gly

100 105 110

Asn Leu Gly Arg Ala Val Phe Gln Ala Lys Lys Arg Val Leu Glu Pro

115 120 125

Leu Gly Leu Val Glu Glu Gly Ala Lys Thr Ala Pro Gly Lys Lys Arg

130 135 140

Pro Val Glu Pro Ser Pro Gln Arg Ser Pro Asp Ser Ser Thr Gly Ile

145 150 155 160

Gly Lys Lys Gly Gln Gln Pro Ala Lys Lys Arg Leu Asn Phe Gly Gln

165 170 175

Thr Gly Asp Ser Glu Ser Val Pro Asp Pro Gln Pro Ile Gly Glu Pro

180 185 190

Pro Ala Gly Pro Ser Gly Leu Gly Ser Gly Thr Met Ala Ala Gly Gly

195 200 205

Gly Ala Pro Met Ala Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Ser

210 215 220

Ser Ser Gly Asn Trp His Cys Asp Ser Thr Trp Leu Gly Asp Arg Val

225 230 235 240

Ile Thr Thr Ser Thr Arg Thr Trp Ala Leu Pro Thr Tyr Asn Asn His

245 250 255

Leu Tyr Lys Gln Ile Ser Asn Gly Thr Ser Gly Gly Ser Thr Asn Asp

260 265 270

Asn Thr Tyr Phe Gly Tyr Ser Thr Pro Trp Gly Tyr Phe Asp Phe Asn

275 280 285

Arg Phe His Cys His Phe Ser Pro Arg Asp Trp Gln Arg Leu Ile Asn

290 295 300

Asn Asn Trp Gly Phe Arg Pro Lys Arg Leu Asn Phe Lys Leu Phe Asn

305 310 315 320

Ile Gln Val Lys Glu Val Thr Gln Asn Glu Gly Thr Lys Thr Ile Ala

325 330 335

Asn Asn Leu Thr Ser Thr Ile Gln Val Phe Thr Asp Ser Glu Tyr Gln

340 345 350

Leu Pro Tyr Val Leu Gly Ser Ala His Gln Gly Cys Leu Pro Pro Phe

355 360 365

Pro Ala Asp Val Phe Met Ile Pro Gln Tyr Gly Tyr Leu Thr Leu Asn

370 375 380

Asn Gly Ser Gln Ala Val Gly Arg Ser Ser Phe Tyr Cys Leu Glu Tyr

385 390 395 400

Phe Pro Ser Gln Met Leu Arg Thr Gly Asn Asn Phe Glu Phe Ser Tyr

405 410 415

Gln Phe Glu Asp Val Pro Phe His Ser Ser Tyr Ala His Ser Gln Ser

420 425 430

Leu Asp Arg Leu Met Asn Pro Leu Ile Asp Gln Tyr Leu Tyr Tyr Leu

435 440 445

Ser Arg Thr Gln Ser Thr Gly Gly Thr Ala Gly Thr Gln Gln Leu Leu

450 455 460

Phe Ser Gln Ala Gly Pro Asn Asn Met Ser Ala Gln Ala Lys Asn Trp

465 470 475 480

Leu Pro Gly Pro Cys Tyr Arg Gln Gln Arg Val Ser Thr Thr Leu Ser

485 490 495

Gln Asn Asn Asn Ser Asn Phe Ala Trp Thr Gly Ala Thr Lys Tyr His

500 505 510

Leu Asn Gly Arg Asp Ser Leu Val Asn Pro Gly Val Ala Met Ala Thr

515 520 525

His Lys Asp Asp Glu Glu Arg Phe Phe Pro Ser Ser Gly Val Leu Met

530 535 540

Phe Gly Lys Gln Gly Ala Gly Lys Asp Asn Val Asp Tyr Ser Ser Val

545 550 555 560

Met Leu Thr Ser Glu Glu Glu Ile Lys Thr Thr Asn Pro Val Ala Thr

565 570 575

Glu Gln Tyr Gly Val Val Ala Asp Asn Leu Gln Gln Gln Asn Ala Ala

580 585 590

Pro Ile Val Gly Ala Val Asn Ser Gln Gly Ala Leu Pro Gly Met Val

595 600 605

Trp Gln Asn Arg Asp Val Tyr Leu Gln Gly Pro Ile Trp Ala Lys Ile

610 615 620

Pro His Thr Asp Gly Asn Phe His Pro Ser Pro Leu Met Gly Gly Phe

625 630 635 640

Gly Leu Lys His Pro Pro Pro Gln Ile Leu Ile Lys Asn Thr Pro Val

645 650 655

Pro Ala Asp Pro Pro Thr Thr Phe Ser Gln Ala Lys Leu Ala Ser Phe

660 665 670

Ile Thr Gln Tyr Ser Thr Gly Gln Val Ser Val Glu Ile Glu Trp Glu

675 680 685

Leu Gln Lys Glu Asn Ser Lys Arg Trp Asn Pro Glu Ile Gln Tyr Thr

690 695 700

Ser Asn Tyr Tyr Lys Ser Thr Asn Val Asp Phe Ala Val Asn Thr Asp

705 710 715 720

Gly Thr Tyr Ser Glu Pro Arg Pro Ile Gly Thr Arg Tyr Leu Thr Arg

725 730 735

Asn Leu

<210> 26

<211> 728

<212> PRT

<213> capsid protein of macaque gland-associated virus, rh.13

<400> 26

Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser

1 5 10 15

Glu Gly Ile Arg Glu Trp Trp Asp Leu Lys Pro Gly Ala Pro Lys Pro

20 25 30

Lys Ala Asn Gln Gln Lys Gln Asp Asp Gly Arg Gly Leu Val Leu Pro

35 40 45

Gly Tyr Lys Tyr Leu Gly Pro Phe Asn Gly Leu Asp Lys Gly Glu Pro

50 55 60

Val Asn Glu Ala Asp Ala Ala Ala Leu Glu His Asp Lys Ala Tyr Asp

65 70 75 80

Lys Gln Leu Glu Gln Gly Asp Asn Pro Tyr Leu Lys Tyr Asn His Ala

85 90 95

Asp Ala Glu Phe Gln Glu Arg Leu Gln Glu Asp Thr Ser Phe Gly Gly

100 105 110

Asn Leu Gly Arg Ala Val Phe Gln Ala Lys Lys Arg Val Leu Glu Pro

115 120 125

Leu Gly Leu Val Glu Glu Gly Ala Lys Thr Ala Pro Gly Lys Lys Arg

130 135 140

Pro Ile Glu Ser Pro Asp Ser Ser Thr Gly Ile Gly Lys Lys Gly Gln

145 150 155 160

Gln Pro Ala Lys Lys Lys Leu Asn Phe Gly Gln Thr Gly Asp Ser Glu

165 170 175

Ser Val Pro Asp Pro Gln Pro Leu Gly Glu Pro Pro Ala Ala Pro Ser

180 185 190

Gly Leu Gly Ser Gly Thr Met Ala Ala Gly Gly Gly Ala Pro Met Ala

195 200 205

Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Asn Ala Ser Gly Asn Trp

210 215 220

His Cys Asp Ser Thr Trp Leu Gly Asp Arg Val Ile Thr Thr Ser Thr

225 230 235 240

Arg Thr Trp Ala Leu Pro Thr Tyr Asn Asn His Leu Tyr Lys Gln Ile

245 250 255

Ser Ser Gln Ser Gly Ala Thr Asn Asp Asn His Phe Phe Gly Tyr Ser

260 265 270

Thr Pro Trp Gly Tyr Phe Asp Phe Asn Arg Phe His Cys His Phe Ser

275 280 285

Pro Arg Asp Trp Gln Arg Leu Ile Asn Asn Asn Trp Gly Phe Arg Pro

290 295 300

Arg Lys Leu Arg Phe Lys Leu Phe Asn Ile Gln Val Lys Glu Val Thr

305 310 315 320

Thr Asn Asp Gly Val Thr Thr Ile Ala Asn Asn Leu Thr Ser Thr Ile

325 330 335

Gln Val Phe Ser Asp Ser Glu Tyr Gln Leu Pro Tyr Val Leu Gly Ser

340 345 350

Ala His Gln Gly Cys Leu Pro Pro Phe Pro Ala Asp Val Phe Met Ile

355 360 365

Pro Gln Tyr Gly Tyr Leu Thr Leu Asn Asn Gly Ser Gln Ser Val Gly

370 375 380

Arg Ser Ser Phe Tyr Cys Leu Glu Tyr Phe Pro Ser Gln Met Leu Arg

385 390 395 400

Thr Gly Asn Asn Phe Glu Phe Ser Tyr Thr Phe Glu Glu Val Pro Phe

405 410 415

His Ser Ser Tyr Ala His Ser Gln Ser Leu Asp Arg Leu Met Asn Pro

420 425 430

Leu Ile Asp Gln Tyr Leu Tyr Tyr Leu Ala Arg Thr Gln Ser Thr Thr

435 440 445

Gly Ser Thr Arg Glu Leu Gln Phe His Gln Ala Gly Pro Asn Thr Met

450 455 460

Ala Glu Gln Ser Lys Asn Trp Leu Pro Gly Pro Cys Tyr Arg Gln Gln

465 470 475 480

Arg Leu Ser Lys Asn Ile Asp Ser Asn Asn Asn Ser Asn Phe Ala Trp

485 490 495

Thr Gly Ala Thr Lys Tyr His Leu Asn Gly Arg Asn Ser Leu Thr Asn

500 505 510

Pro Gly Val Ala Met Ala Thr Asn Lys Asp Asp Glu Asp Gln Phe Phe

515 520 525

Pro Ile Asn Gly Val Leu Val Phe Gly Glu Thr Gly Ala Ala Asn Lys

530 535 540

Thr Thr Leu Glu Asn Val Leu Met Thr Ser Glu Glu Glu Ile Lys Thr

545 550 555 560

Thr Asn Pro Val Ala Thr Glu Glu Tyr Gly Val Val Ser Ser Asn Leu

565 570 575

Gln Ser Ser Thr Ala Gly Pro Gln Thr Gln Thr Val Asn Ser Gln Gly

580 585 590

Ala Leu Pro Gly Met Val Trp Gln Asn Arg Asp Val Tyr Leu Gln Gly

595 600 605

Pro Ile Trp Ala Lys Ile Pro His Thr Asp Gly Asn Phe His Pro Ser

610 615 620

Pro Leu Met Gly Gly Phe Gly Leu Lys His Pro Pro Pro Gln Ile Leu

625 630 635 640

Ile Lys Asn Thr Pro Val Pro Ala Asn Pro Pro Glu Val Phe Thr Pro

645 650 655

Ala Lys Phe Ala Ser Phe Ile Thr Gln Tyr Ser Thr Gly Gln Val Ser

660 665 670

Val Glu Ile Glu Trp Glu Leu Gln Lys Glu Asn Ser Lys Arg Trp Asn

675 680 685

Pro Glu Ile Gln Tyr Thr Ser Asn Tyr Ala Lys Ser Asn Asn Val Glu

690 695 700

Phe Ala Val Asn Asn Glu Gly Val Tyr Thr Glu Pro Arg Pro Ile Gly

705 710 715 720

Thr Arg Tyr Leu Thr Arg Asn Leu

725

<210> 27

<211> 736

<212> PRT

<213> capsid protein of adeno-associated virus serotype 1

<400> 27

Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser

1 5 10 15

Glu Gly Ile Arg Glu Trp Trp Asp Leu Lys Pro Gly Ala Pro Lys Pro

20 25 30

Lys Ala Asn Gln Gln Lys Gln Asp Asp Gly Arg Gly Leu Val Leu Pro

35 40 45

Gly Tyr Lys Tyr Leu Gly Pro Phe Asn Gly Leu Asp Lys Gly Glu Pro

50 55 60

Val Asn Ala Ala Asp Ala Ala Ala Leu Glu His Asp Lys Ala Tyr Asp

65 70 75 80

Gln Gln Leu Lys Ala Gly Asp Asn Pro Tyr Leu Arg Tyr Asn His Ala

85 90 95

Asp Ala Glu Phe Gln Glu Arg Leu Gln Glu Asp Thr Ser Phe Gly Gly

100 105 110

Asn Leu Gly Arg Ala Val Phe Gln Ala Lys Lys Arg Val Leu Glu Pro

115 120 125

Leu Gly Leu Val Glu Glu Gly Ala Lys Thr Ala Pro Gly Lys Lys Arg

130 135 140

Pro Val Glu Gln Ser Pro Gln Glu Pro Asp Ser Ser Ser Gly Ile Gly

145 150 155 160

Lys Thr Gly Gln Gln Pro Ala Lys Lys Arg Leu Asn Phe Gly Gln Thr

165 170 175

Gly Asp Ser Glu Ser Val Pro Asp Pro Gln Pro Leu Gly Glu Pro Pro

180 185 190

Ala Thr Pro Ala Ala Val Gly Pro Thr Thr Met Ala Ser Gly Gly Gly

195 200 205

Ala Pro Met Ala Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Asn Ala

210 215 220

Ser Gly Asn Trp His Cys Asp Ser Thr Trp Leu Gly Asp Arg Val Ile

225 230 235 240

Thr Thr Ser Thr Arg Thr Trp Ala Leu Pro Thr Tyr Asn Asn His Leu

245 250 255

Tyr Lys Gln Ile Ser Ser Ala Ser Thr Gly Ala Ser Asn Asp Asn His

260 265 270

Tyr Phe Gly Tyr Ser Thr Pro Trp Gly Tyr Phe Asp Phe Asn Arg Phe

275 280 285

His Cys His Phe Ser Pro Arg Asp Trp Gln Arg Leu Ile Asn Asn Asn

290 295 300

Trp Gly Phe Arg Pro Lys Arg Leu Asn Phe Lys Leu Phe Asn Ile Gln

305 310 315 320

Val Lys Glu Val Thr Thr Asn Asp Gly Val Thr Thr Ile Ala Asn Asn

325 330 335

Leu Thr Ser Thr Val Gln Val Phe Ser Asp Ser Glu Tyr Gln Leu Pro

340 345 350

Tyr Val Leu Gly Ser Ala His Gln Gly Cys Leu Pro Pro Phe Pro Ala

355 360 365

Asp Val Phe Met Ile Pro Gln Tyr Gly Tyr Leu Thr Leu Asn Asn Gly

370 375 380

Ser Gln Ala Val Gly Arg Ser Ser Phe Tyr Cys Leu Glu Tyr Phe Pro

385 390 395 400

Ser Gln Met Leu Arg Thr Gly Asn Asn Phe Thr Phe Ser Tyr Thr Phe

405 410 415

Glu Glu Val Pro Phe His Ser Ser Tyr Ala His Ser Gln Ser Leu Asp

420 425 430

Arg Leu Met Asn Pro Leu Ile Asp Gln Tyr Leu Tyr Tyr Leu Asn Arg

435 440 445

Thr Gln Asn Gln Ser Gly Ser Ala Gln Asn Lys Asp Leu Leu Phe Ser

450 455 460

Arg Gly Ser Pro Ala Gly Met Ser Val Gln Pro Lys Asn Trp Leu Pro

465 470 475 480

Gly Pro Cys Tyr Arg Gln Gln Arg Val Ser Lys Thr Lys Thr Asp Asn

485 490 495

Asn Asn Ser Asn Phe Thr Trp Thr Gly Ala Ser Lys Tyr Asn Leu Asn

500 505 510

Gly Arg Glu Ser Ile Ile Asn Pro Gly Thr Ala Met Ala Ser His Lys

515 520 525

Asp Asp Glu Asp Lys Phe Phe Pro Met Ser Gly Val Met Ile Phe Gly

530 535 540

Lys Glu Ser Ala Gly Ala Ser Asn Thr Ala Leu Asp Asn Val Met Ile

545 550 555 560

Thr Asp Glu Glu Glu Ile Lys Ala Thr Asn Pro Val Ala Thr Glu Arg

565 570 575

Phe Gly Thr Val Ala Val Asn Phe Gln Ser Ser Ser Thr Asp Pro Ala

580 585 590

Thr Gly Asp Val His Ala Met Gly Ala Leu Pro Gly Met Val Trp Gln

595 600 605

Asp Arg Asp Val Tyr Leu Gln Gly Pro Ile Trp Ala Lys Ile Pro His

610 615 620

Thr Asp Gly His Phe His Pro Ser Pro Leu Met Gly Gly Phe Gly Leu

625 630 635 640

Lys Asn Pro Pro Pro Gln Ile Leu Ile Lys Asn Thr Pro Val Pro Ala

645 650 655

Asn Pro Pro Ala Glu Phe Ser Ala Thr Lys Phe Ala Ser Phe Ile Thr

660 665 670

Gln Tyr Ser Thr Gly Gln Val Ser Val Glu Ile Glu Trp Glu Leu Gln

675 680 685

Lys Glu Asn Ser Lys Arg Trp Asn Pro Glu Val Gln Tyr Thr Ser Asn

690 695 700

Tyr Ala Lys Ser Ala Asn Val Asp Phe Thr Val Asp Asn Asn Gly Leu

705 710 715 720

Tyr Thr Glu Pro Arg Pro Ile Gly Thr Arg Tyr Leu Thr Arg Pro Leu

725 730 735

<210> 28

<211> 736

<212> PRT

<213> capsid protein of adeno-associated virus serotype 3

<400> 28

Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser

1 5 10 15

Glu Gly Ile Arg Glu Trp Trp Ala Leu Lys Pro Gly Val Pro Gln Pro

20 25 30

Lys Ala Asn Gln Gln His Gln Asp Asn Arg Arg Gly Leu Val Leu Pro

35 40 45

Gly Tyr Lys Tyr Leu Gly Pro Gly Asn Gly Leu Asp Lys Gly Glu Pro

50 55 60

Val Asn Glu Ala Asp Ala Ala Ala Leu Glu His Asp Lys Ala Tyr Asp

65 70 75 80

Gln Gln Leu Lys Ala Gly Asp Asn Pro Tyr Leu Lys Tyr Asn His Ala

85 90 95

Asp Ala Glu Phe Gln Glu Arg Leu Gln Glu Asp Thr Ser Phe Gly Gly

100 105 110

Asn Leu Gly Arg Ala Val Phe Gln Ala Lys Lys Arg Ile Leu Glu Pro

115 120 125

Leu Gly Leu Val Glu Glu Ala Ala Lys Thr Ala Pro Gly Lys Lys Gly

130 135 140

Ala Val Asp Gln Ser Pro Gln Glu Pro Asp Ser Ser Ser Gly Val Gly

145 150 155 160

Lys Ser Gly Lys Gln Pro Ala Arg Lys Arg Leu Asn Phe Gly Gln Thr

165 170 175

Gly Asp Ser Glu Ser Val Pro Asp Pro Gln Pro Leu Gly Glu Pro Pro

180 185 190

Ala Ala Pro Thr Ser Leu Gly Ser Asn Thr Met Ala Ser Gly Gly Gly

195 200 205

Ala Pro Met Ala Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Asn Ser

210 215 220

Ser Gly Asn Trp His Cys Asp Ser Gln Trp Leu Gly Asp Arg Val Ile

225 230 235 240

Thr Thr Ser Thr Arg Thr Trp Ala Leu Pro Thr Tyr Asn Asn His Leu

245 250 255

Tyr Lys Gln Ile Ser Ser Gln Ser Gly Ala Ser Asn Asp Asn His Tyr

260 265 270

Phe Gly Tyr Ser Thr Pro Trp Gly Tyr Phe Asp Phe Asn Arg Phe His

275 280 285

Cys His Phe Ser Pro Arg Asp Trp Gln Arg Leu Ile Asn Asn Asn Trp

290 295 300

Gly Phe Arg Pro Lys Lys Leu Ser Phe Lys Leu Phe Asn Ile Gln Val

305 310 315 320

Arg Gly Val Thr Gln Asn Asp Gly Thr Thr Thr Ile Ala Asn Asn Leu

325 330 335

Thr Ser Thr Val Gln Val Phe Thr Asp Ser Glu Tyr Gln Leu Pro Tyr

340 345 350

Val Leu Gly Ser Ala His Gln Gly Cys Leu Pro Pro Phe Pro Ala Asp

355 360 365

Val Phe Met Val Pro Gln Tyr Gly Tyr Leu Thr Leu Asn Asn Gly Ser

370 375 380

Gln Ala Val Gly Arg Ser Ser Phe Tyr Cys Leu Glu Tyr Phe Pro Ser

385 390 395 400

Gln Met Leu Arg Thr Gly Asn Asn Phe Gln Phe Ser Tyr Thr Phe Glu

405 410 415

Asp Val Pro Phe His Ser Ser Tyr Ala His Ser Gln Ser Leu Asp Arg

420 425 430

Leu Met Asn Pro Leu Ile Asp Gln Tyr Leu Tyr Tyr Leu Asn Arg Thr

435 440 445

Gln Gly Thr Thr Ser Gly Thr Thr Asn Gln Ser Arg Leu Leu Phe Ser

450 455 460

Gln Ala Gly Pro Gln Ser Met Ser Leu Gln Ala Arg Asn Trp Leu Pro

465 470 475 480

Gly Pro Cys Tyr Arg Gln Gln Arg Leu Ser Lys Thr Ala Asn Asp Asn

485 490 495

Asn Asn Ser Asn Phe Pro Trp Thr Ala Ala Ser Lys Tyr His Leu Asn

500 505 510

Gly Arg Asp Ser Leu Val Asn Pro Gly Pro Ala Met Ala Ser His Lys

515 520 525

Asp Asp Glu Glu Lys Phe Phe Pro Met His Gly Asn Leu Ile Phe Gly

530 535 540

Lys Glu Gly Thr Thr Ala Ser Asn Ala Glu Leu Asp Asn Val Met Ile

545 550 555 560

Thr Asp Glu Glu Glu Ile Arg Thr Thr Asn Pro Val Ala Thr Glu Gln

565 570 575

Tyr Gly Thr Val Ala Asn Asn Leu Gln Ser Ser Asn Thr Ala Pro Thr

580 585 590

Thr Gly Thr Val Asn His Gln Gly Ala Leu Pro Gly Met Val Trp Gln

595 600 605

Asp Arg Asp Val Tyr Leu Gln Gly Pro Ile Trp Ala Lys Ile Pro His

610 615 620

Thr Asp Gly His Phe His Pro Ser Pro Leu Met Gly Gly Phe Gly Leu

625 630 635 640

Lys His Pro Pro Pro Gln Ile Met Ile Lys Asn Thr Pro Val Pro Ala

645 650 655

Asn Pro Pro Thr Thr Phe Ser Pro Ala Lys Phe Ala Ser Phe Ile Thr

660 665 670

Gln Tyr Ser Thr Gly Gln Val Ser Val Glu Ile Glu Trp Glu Leu Gln

675 680 685

Lys Glu Asn Ser Lys Arg Trp Asn Pro Glu Ile Gln Tyr Thr Ser Asn

690 695 700

Tyr Asn Lys Ser Val Asn Val Asp Phe Thr Val Asp Thr Asn Gly Val

705 710 715 720

Tyr Ser Glu Pro Arg Pro Ile Gly Thr Arg Tyr Leu Thr Arg Asn Leu

725 730 735

<210> 29

<211> 736

<212> PRT

<213> capsid protein of adeno-associated virus serotype 6

<400> 29

Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser

1 5 10 15

Glu Gly Ile Arg Glu Trp Trp Asp Leu Lys Pro Gly Ala Pro Lys Pro

20 25 30

Lys Ala Asn Gln Gln Lys Gln Asp Asp Gly Arg Gly Leu Val Leu Pro

35 40 45

Gly Tyr Lys Tyr Leu Gly Pro Phe Asn Gly Leu Asp Lys Gly Glu Pro

50 55 60

Val Asn Ala Ala Asp Ala Ala Ala Leu Glu His Asp Lys Ala Tyr Asp

65 70 75 80

Gln Gln Leu Lys Ala Gly Asp Asn Pro Tyr Leu Arg Tyr Asn His Ala

85 90 95

Asp Ala Glu Phe Gln Glu Arg Leu Gln Glu Asp Thr Ser Phe Gly Gly

100 105 110

Asn Leu Gly Arg Ala Val Phe Gln Ala Lys Lys Arg Val Leu Glu Pro

115 120 125

Phe Gly Leu Val Glu Glu Gly Ala Lys Thr Ala Pro Gly Lys Lys Arg

130 135 140

Pro Val Glu Gln Ser Pro Gln Glu Pro Asp Ser Ser Ser Gly Ile Gly

145 150 155 160

Lys Thr Gly Gln Gln Pro Ala Lys Lys Arg Leu Asn Phe Gly Gln Thr

165 170 175

Gly Asp Ser Glu Ser Val Pro Asp Pro Gln Pro Leu Gly Glu Pro Pro

180 185 190

Ala Thr Pro Ala Ala Val Gly Pro Thr Thr Met Ala Ser Gly Gly Gly

195 200 205

Ala Pro Met Ala Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Asn Ala

210 215 220

Ser Gly Asn Trp His Cys Asp Ser Thr Trp Leu Gly Asp Arg Val Ile

225 230 235 240

Thr Thr Ser Thr Arg Thr Trp Ala Leu Pro Thr Tyr Asn Asn His Leu

245 250 255

Tyr Lys Gln Ile Ser Ser Ala Ser Thr Gly Ala Ser Asn Asp Asn His

260 265 270

Tyr Phe Gly Tyr Ser Thr Pro Trp Gly Tyr Phe Asp Phe Asn Arg Phe

275 280 285

His Cys His Phe Ser Pro Arg Asp Trp Gln Arg Leu Ile Asn Asn Asn

290 295 300

Trp Gly Phe Arg Pro Lys Arg Leu Asn Phe Lys Leu Phe Asn Ile Gln

305 310 315 320

Val Lys Glu Val Thr Thr Asn Asp Gly Val Thr Thr Ile Ala Asn Asn

325 330 335

Leu Thr Ser Thr Val Gln Val Phe Ser Asp Ser Glu Tyr Gln Leu Pro

340 345 350

Tyr Val Leu Gly Ser Ala His Gln Gly Cys Leu Pro Pro Phe Pro Ala

355 360 365

Asp Val Phe Met Ile Pro Gln Tyr Gly Tyr Leu Thr Leu Asn Asn Gly

370 375 380

Ser Gln Ala Val Gly Arg Ser Ser Phe Tyr Cys Leu Glu Tyr Phe Pro

385 390 395 400

Ser Gln Met Leu Arg Thr Gly Asn Asn Phe Thr Phe Ser Tyr Thr Phe

405 410 415

Glu Asp Val Pro Phe His Ser Ser Tyr Ala His Ser Gln Ser Leu Asp

420 425 430

Arg Leu Met Asn Pro Leu Ile Asp Gln Tyr Leu Tyr Tyr Leu Asn Arg

435 440 445

Thr Gln Asn Gln Ser Gly Ser Ala Gln Asn Lys Asp Leu Leu Phe Ser

450 455 460

Arg Gly Ser Pro Ala Gly Met Ser Val Gln Pro Lys Asn Trp Leu Pro

465 470 475 480

Gly Pro Cys Tyr Arg Gln Gln Arg Val Ser Lys Thr Lys Thr Asp Asn

485 490 495

Asn Asn Ser Asn Phe Thr Trp Thr Gly Ala Ser Lys Tyr Asn Leu Asn

500 505 510

Gly Arg Glu Ser Ile Ile Asn Pro Gly Thr Ala Met Ala Ser His Lys

515 520 525

Asp Asp Lys Asp Lys Phe Phe Pro Met Ser Gly Val Met Ile Phe Gly

530 535 540

Lys Glu Ser Ala Gly Ala Ser Asn Thr Ala Leu Asp Asn Val Met Ile

545 550 555 560

Thr Asp Glu Glu Glu Ile Lys Ala Thr Asn Pro Val Ala Thr Glu Arg

565 570 575

Phe Gly Thr Val Ala Val Asn Leu Gln Ser Ser Ser Thr Asp Pro Ala

580 585 590

Thr Gly Asp Val His Val Met Gly Ala Leu Pro Gly Met Val Trp Gln

595 600 605

Asp Arg Asp Val Tyr Leu Gln Gly Pro Ile Trp Ala Lys Ile Pro His

610 615 620

Thr Asp Gly His Phe His Pro Ser Pro Leu Met Gly Gly Phe Gly Leu

625 630 635 640

Lys His Pro Pro Pro Gln Ile Leu Ile Lys Asn Thr Pro Val Pro Ala

645 650 655

Asn Pro Pro Ala Glu Phe Ser Ala Thr Lys Phe Ala Ser Phe Ile Thr

660 665 670

Gln Tyr Ser Thr Gly Gln Val Ser Val Glu Ile Glu Trp Glu Leu Gln

675 680 685

Lys Glu Asn Ser Lys Arg Trp Asn Pro Glu Val Gln Tyr Thr Ser Asn

690 695 700

Tyr Ala Lys Ser Ala Asn Val Asp Phe Thr Val Asp Asn Asn Gly Leu

705 710 715 720

Tyr Thr Glu Pro Arg Pro Ile Gly Thr Arg Tyr Leu Thr Arg Pro Leu

725 730 735

<210> 30

<211> 737

<212> PRT

<213> capsid protein of adeno-associated virus serotype 7

<400> 30

Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser

1 5 10 15

Glu Gly Ile Arg Glu Trp Trp Asp Leu Lys Pro Gly Ala Pro Lys Pro

20 25 30

Lys Ala Asn Gln Gln Lys Gln Asp Asn Gly Arg Gly Leu Val Leu Pro

35 40 45

Gly Tyr Lys Tyr Leu Gly Pro Phe Asn Gly Leu Asp Lys Gly Glu Pro

50 55 60

Val Asn Ala Ala Asp Ala Ala Ala Leu Glu His Asp Lys Ala Tyr Asp

65 70 75 80

Gln Gln Leu Lys Ala Gly Asp Asn Pro Tyr Leu Arg Tyr Asn His Ala

85 90 95

Asp Ala Glu Phe Gln Glu Arg Leu Gln Glu Asp Thr Ser Phe Gly Gly

100 105 110

Asn Leu Gly Arg Ala Val Phe Gln Ala Lys Lys Arg Val Leu Glu Pro

115 120 125

Leu Gly Leu Val Glu Glu Gly Ala Lys Thr Ala Pro Ala Lys Lys Arg

130 135 140

Pro Val Glu Pro Ser Pro Gln Arg Ser Pro Asp Ser Ser Thr Gly Ile

145 150 155 160

Gly Lys Lys Gly Gln Gln Pro Ala Arg Lys Arg Leu Asn Phe Gly Gln

165 170 175

Thr Gly Asp Ser Glu Ser Val Pro Asp Pro Gln Pro Leu Gly Glu Pro

180 185 190

Pro Ala Ala Pro Ser Ser Val Gly Ser Gly Thr Val Ala Ala Gly Gly

195 200 205

Gly Ala Pro Met Ala Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Asn

210 215 220

Ala Ser Gly Asn Trp His Cys Asp Ser Thr Trp Leu Gly Asp Arg Val

225 230 235 240

Ile Thr Thr Ser Thr Arg Thr Trp Ala Leu Pro Thr Tyr Asn Asn His

245 250 255

Leu Tyr Lys Gln Ile Ser Ser Glu Thr Ala Gly Ser Thr Asn Asp Asn

260 265 270

Thr Tyr Phe Gly Tyr Ser Thr Pro Trp Gly Tyr Phe Asp Phe Asn Arg

275 280 285

Phe His Cys His Phe Ser Pro Arg Asp Trp Gln Arg Leu Ile Asn Asn

290 295 300

Asn Trp Gly Phe Arg Pro Lys Lys Leu Arg Phe Lys Leu Phe Asn Ile

305 310 315 320

Gln Val Lys Glu Val Thr Thr Asn Asp Gly Val Thr Thr Ile Ala Asn

325 330 335

Asn Leu Thr Ser Thr Ile Gln Val Phe Ser Asp Ser Glu Tyr Gln Leu

340 345 350

Pro Tyr Val Leu Gly Ser Ala His Gln Gly Cys Leu Pro Pro Phe Pro

355 360 365

Ala Asp Val Phe Met Ile Pro Gln Tyr Gly Tyr Leu Thr Leu Asn Asn

370 375 380

Gly Ser Gln Ser Val Gly Arg Ser Ser Phe Tyr Cys Leu Glu Tyr Phe

385 390 395 400

Pro Ser Gln Met Leu Arg Thr Gly Asn Asn Phe Glu Phe Ser Tyr Ser

405 410 415

Phe Glu Asp Val Pro Phe His Ser Ser Tyr Ala His Ser Gln Ser Leu

420 425 430

Asp Arg Leu Met Asn Pro Leu Ile Asp Gln Tyr Leu Tyr Tyr Leu Ala

435 440 445

Arg Thr Gln Ser Asn Pro Gly Gly Thr Ala Gly Asn Arg Glu Leu Gln

450 455 460

Phe Tyr Gln Gly Gly Pro Ser Thr Met Ala Glu Gln Ala Lys Asn Trp

465 470 475 480

Leu Pro Gly Pro Cys Phe Arg Gln Gln Arg Val Ser Lys Thr Leu Asp

485 490 495

Gln Asn Asn Asn Ser Asn Phe Ala Trp Thr Gly Ala Thr Lys Tyr His

500 505 510

Leu Asn Gly Arg Asn Ser Leu Val Asn Pro Gly Val Ala Met Ala Thr

515 520 525

His Lys Asp Asp Glu Asp Arg Phe Phe Pro Ser Ser Gly Val Leu Ile

530 535 540

Phe Gly Lys Thr Gly Ala Thr Asn Lys Thr Thr Leu Glu Asn Val Leu

545 550 555 560

Met Thr Asn Glu Glu Glu Ile Arg Pro Thr Asn Pro Val Ala Thr Glu

565 570 575

Glu Tyr Gly Ile Val Ser Ser Asn Leu Gln Ala Ala Asn Thr Ala Ala

580 585 590

Gln Thr Gln Val Val Asn Asn Gln Gly Ala Leu Pro Gly Met Val Trp

595 600 605

Gln Asn Arg Asp Val Tyr Leu Gln Gly Pro Ile Trp Ala Lys Ile Pro

610 615 620

His Thr Asp Gly Asn Phe His Pro Ser Pro Leu Met Gly Gly Phe Gly

625 630 635 640

Leu Lys His Pro Pro Pro Gln Ile Leu Ile Lys Asn Thr Pro Val Pro

645 650 655

Ala Asn Pro Pro Glu Val Phe Thr Pro Ala Lys Phe Ala Ser Phe Ile

660 665 670

Thr Gln Tyr Ser Thr Gly Gln Val Ser Val Glu Ile Glu Trp Glu Leu

675 680 685

Gln Lys Glu Asn Ser Lys Arg Trp Asn Pro Glu Ile Gln Tyr Thr Ser

690 695 700

Asn Phe Glu Lys Gln Thr Gly Val Asp Phe Ala Val Asp Ser Gln Gly

705 710 715 720

Val Tyr Ser Glu Pro Arg Pro Ile Gly Thr Arg Tyr Leu Thr Arg Asn

725 730 735

Leu

<210> 31

<211> 738

<212> PRT

<213> capsid protein of adeno-associated virus serotype 8

<400> 31

Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser

1 5 10 15

Glu Gly Ile Arg Glu Trp Trp Ala Leu Lys Pro Gly Ala Pro Lys Pro

20 25 30

Lys Ala Asn Gln Gln Lys Gln Asp Asp Gly Arg Gly Leu Val Leu Pro

35 40 45

Gly Tyr Lys Tyr Leu Gly Pro Phe Asn Gly Leu Asp Lys Gly Glu Pro

50 55 60

Val Asn Ala Ala Asp Ala Ala Ala Leu Glu His Asp Lys Ala Tyr Asp

65 70 75 80

Gln Gln Leu Gln Ala Gly Asp Asn Pro Tyr Leu Arg Tyr Asn His Ala

85 90 95

Asp Ala Glu Phe Gln Glu Arg Leu Gln Glu Asp Thr Ser Phe Gly Gly

100 105 110

Asn Leu Gly Arg Ala Val Phe Gln Ala Lys Lys Arg Val Leu Glu Pro

115 120 125

Leu Gly Leu Val Glu Glu Gly Ala Lys Thr Ala Pro Gly Lys Lys Arg

130 135 140

Pro Val Glu Pro Ser Pro Gln Arg Ser Pro Asp Ser Ser Thr Gly Ile

145 150 155 160

Gly Lys Lys Gly Gln Gln Pro Ala Arg Lys Arg Leu Asn Phe Gly Gln

165 170 175

Thr Gly Asp Ser Glu Ser Val Pro Asp Pro Gln Pro Leu Gly Glu Pro

180 185 190

Pro Ala Ala Pro Ser Gly Val Gly Pro Asn Thr Met Ala Ala Gly Gly

195 200 205

Gly Ala Pro Met Ala Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Ser

210 215 220

Ser Ser Gly Asn Trp His Cys Asp Ser Thr Trp Leu Gly Asp Arg Val

225 230 235 240

Ile Thr Thr Ser Thr Arg Thr Trp Ala Leu Pro Thr Tyr Asn Asn His

245 250 255

Leu Tyr Lys Gln Ile Ser Asn Gly Thr Ser Gly Gly Ala Thr Asn Asp

260 265 270

Asn Thr Tyr Phe Gly Tyr Ser Thr Pro Trp Gly Tyr Phe Asp Phe Asn

275 280 285

Arg Phe His Cys His Phe Ser Pro Arg Asp Trp Gln Arg Leu Ile Asn

290 295 300

Asn Asn Trp Gly Phe Arg Pro Lys Arg Leu Ser Phe Lys Leu Phe Asn

305 310 315 320

Ile Gln Val Lys Glu Val Thr Gln Asn Glu Gly Thr Lys Thr Ile Ala

325 330 335

Asn Asn Leu Thr Ser Thr Ile Gln Val Phe Thr Asp Ser Glu Tyr Gln

340 345 350

Leu Pro Tyr Val Leu Gly Ser Ala His Gln Gly Cys Leu Pro Pro Phe

355 360 365

Pro Ala Asp Val Phe Met Ile Pro Gln Tyr Gly Tyr Leu Thr Leu Asn

370 375 380

Asn Gly Ser Gln Ala Val Gly Arg Ser Ser Phe Tyr Cys Leu Glu Tyr

385 390 395 400

Phe Pro Ser Gln Met Leu Arg Thr Gly Asn Asn Phe Gln Phe Thr Tyr

405 410 415

Thr Phe Glu Asp Val Pro Phe His Ser Ser Tyr Ala His Ser Gln Ser

420 425 430

Leu Asp Arg Leu Met Asn Pro Leu Ile Asp Gln Tyr Leu Tyr Tyr Leu

435 440 445

Ser Arg Thr Gln Thr Thr Gly Gly Thr Ala Asn Thr Gln Thr Leu Gly

450 455 460

Phe Ser Gln Gly Gly Pro Asn Thr Met Ala Asn Gln Ala Lys Asn Trp

465 470 475 480

Leu Pro Gly Pro Cys Tyr Arg Gln Gln Arg Val Ser Thr Thr Thr Gly

485 490 495

Gln Asn Asn Asn Ser Asn Phe Ala Trp Thr Ala Gly Thr Lys Tyr His

500 505 510

Leu Asn Gly Arg Asn Ser Leu Ala Asn Pro Gly Ile Ala Met Ala Thr

515 520 525

His Lys Asp Asp Glu Glu Arg Phe Phe Pro Ser Asn Gly Ile Leu Ile

530 535 540

Phe Gly Lys Gln Asn Ala Ala Arg Asp Asn Ala Asp Tyr Ser Asp Val

545 550 555 560

Met Leu Thr Ser Glu Glu Glu Ile Lys Thr Thr Asn Pro Val Ala Thr

565 570 575

Glu Glu Tyr Gly Ile Val Ala Asp Asn Leu Gln Gln Gln Asn Thr Ala

580 585 590

Pro Gln Ile Gly Thr Val Asn Ser Gln Gly Ala Leu Pro Gly Met Val

595 600 605

Trp Gln Asn Arg Asp Val Tyr Leu Gln Gly Pro Ile Trp Ala Lys Ile

610 615 620

Pro His Thr Asp Gly Asn Phe His Pro Ser Pro Leu Met Gly Gly Phe

625 630 635 640

Gly Leu Lys His Pro Pro Pro Gln Ile Leu Ile Lys Asn Thr Pro Val

645 650 655

Pro Ala Asp Pro Pro Thr Thr Phe Asn Gln Ser Lys Leu Asn Ser Phe

660 665 670

Ile Thr Gln Tyr Ser Thr Gly Gln Val Ser Val Glu Ile Glu Trp Glu

675 680 685

Leu Gln Lys Glu Asn Ser Lys Arg Trp Asn Pro Glu Ile Gln Tyr Thr

690 695 700

Ser Asn Tyr Tyr Lys Ser Thr Ser Val Asp Phe Ala Val Asn Thr Glu

705 710 715 720

Gly Val Tyr Ser Glu Pro Arg Pro Ile Gly Thr Arg Tyr Leu Thr Arg

725 730 735

Asn Leu

<210> 32

<211> 735

<212> PRT

<213> capsid protein of adeno-associated virus, hu.13

<400> 32

Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Thr Leu Ser

1 5 10 15

Glu Gly Ile Arg Gln Trp Trp Lys Leu Lys Pro Gly Pro Pro Pro Pro

20 25 30

Lys Pro Ala Glu Arg His Lys Asp Asp Ser Arg Gly Leu Val Leu Pro

35 40 45

Gly Tyr Lys Tyr Leu Gly Pro Phe Asn Gly Leu Asp Lys Gly Glu Pro

50 55 60

Val Asn Glu Ala Asp Ala Ala Ala Leu Glu His Asp Lys Ala Tyr Asp

65 70 75 80

Arg Gln Leu Asp Ser Gly Asp Asn Pro Tyr Leu Lys Tyr Asn His Ala

85 90 95

Asp Ala Glu Phe Gln Glu Arg Leu Lys Glu Asp Thr Ser Phe Gly Gly

100 105 110

Asn Leu Gly Arg Ala Val Phe Gln Ala Lys Lys Arg Val Leu Glu Pro

115 120 125

Leu Gly Leu Val Glu Glu Pro Val Lys Thr Ala Pro Gly Lys Lys Arg

130 135 140

Pro Val Glu His Ser Pro Ala Glu Pro Asp Ser Ser Ser Gly Thr Gly

145 150 155 160

Lys Ala Gly Gln Gln Pro Ala Arg Lys Arg Leu Asn Phe Gly Gln Thr

165 170 175

Gly Asp Ala Asp Ser Val Pro Asp Pro Gln Pro Leu Gly Gln Pro Pro

180 185 190

Ala Ala Pro Ser Gly Leu Gly Thr Asn Thr Met Ala Ser Gly Ser Gly

195 200 205

Ala Pro Met Ala Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Asn Ser

210 215 220

Ser Gly Asn Trp His Cys Asp Ser Thr Trp Met Gly Asp Arg Val Ile

225 230 235 240

Thr Thr Ser Thr Arg Thr Trp Ala Leu Pro Thr Tyr Asn Asn His Leu

245 250 255

Tyr Lys Gln Ile Ser Ser Gln Ser Gly Ala Ser Asn Asp Asn His Tyr

260 265 270

Phe Gly Tyr Ser Thr Pro Trp Gly Tyr Phe Asp Phe Asn Arg Phe His

275 280 285

Cys His Phe Ser Pro Arg Asp Trp Gln Arg Leu Ile Asn Asn Asn Trp

290 295 300

Gly Phe Arg Pro Lys Arg Leu Asn Phe Lys Leu Phe Asn Ile Gln Val

305 310 315 320

Lys Glu Val Thr Gln Asn Asp Gly Thr Thr Thr Ile Ala Asn Asn Leu

325 330 335

Thr Ser Thr Val Gln Val Phe Thr Asp Ser Glu Tyr Gln Leu Pro Tyr

340 345 350

Val Leu Gly Ser Ala His Gln Gly Cys Leu Pro Pro Phe Pro Ala Asp

355 360 365

Val Phe Met Val Pro Gln Tyr Gly Tyr Leu Thr Leu Asn Asn Gly Ser

370 375 380

Gln Ala Val Gly Arg Ser Ser Phe Tyr Cys Leu Glu Tyr Phe Pro Ser

385 390 395 400

Gln Met Leu Arg Thr Gly Asn Asn Phe Thr Phe Ser Tyr Thr Phe Glu

405 410 415

Asp Val Pro Phe His Ser Ser Tyr Ala His Ser Gln Ser Leu Asp Arg

420 425 430

Leu Met Asn Pro Leu Ile Asp Gln Tyr Leu Tyr Tyr Leu Ser Arg Thr

435 440 445

Asn Thr Pro Ser Gly Thr Thr Thr Gln Ser Arg Leu Gln Phe Ser Gln

450 455 460

Ala Gly Ala Ser Asp Ile Arg Asp Gln Ser Arg Asn Trp Leu Pro Gly

465 470 475 480

Pro Cys Tyr Arg Gln Gln Arg Val Ser Lys Thr Ser Ala Asp Asn Asn

485 490 495

Asn Ser Glu Tyr Ser Trp Thr Gly Ala Thr Lys Tyr His Leu Asn Gly

500 505 510

Arg Asp Ser Leu Val Asn Pro Gly Pro Ala Met Ala Ser His Lys Asp

515 520 525

Asp Glu Glu Lys Phe Phe Pro Gln Ser Gly Val Leu Ile Phe Gly Lys

530 535 540

Gln Gly Ser Glu Lys Thr Asn Val Asp Ile Glu Lys Val Met Ile Thr

545 550 555 560

Asp Glu Glu Glu Ile Arg Thr Thr Asn Pro Val Ala Thr Glu Gln Tyr

565 570 575

Gly Ser Val Ser Thr Asn Leu Gln Gly Gly Asn Thr Gln Ala Ala Thr

580 585 590

Ala Asp Val Asn Thr Gln Gly Val Leu Pro Gly Met Val Trp Gln Asp

595 600 605

Arg Asp Val Tyr Leu Gln Gly Pro Ile Trp Ala Lys Ile Pro His Thr

610 615 620

Asp Gly His Phe His Pro Ser Pro Leu Met Gly Gly Phe Gly Leu Lys

625 630 635 640

His Pro Pro Pro Gln Ile Leu Ile Lys Asn Thr Pro Val Pro Ala Asn

645 650 655

Pro Ser Thr Thr Phe Ser Ala Ala Lys Phe Ala Ser Phe Ile Thr Gln

660 665 670

Tyr Ser Thr Gly Gln Val Ser Val Glu Ile Glu Trp Glu Leu Gln Lys

675 680 685

Glu Asn Ser Lys Arg Trp Asn Pro Glu Ile Gln Tyr Thr Ser Asn Tyr

690 695 700

Asn Lys Ser Val Asn Val Asp Phe Thr Val Asp Thr Asn Gly Val Tyr

705 710 715 720

Ser Glu Pro Arg Pro Ile Gly Thr Arg Tyr Leu Thr Arg Asn Leu

725 730 735

<210> 33

<211> 735

<212> PRT

<213> capsid protein of adeno-associated virus, hu.26

<400> 33

Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Thr Leu Ser

1 5 10 15

Glu Gly Ile Arg Gln Trp Trp Lys Leu Lys Pro Gly Pro Pro Pro Pro

20 25 30

Lys Pro Ala Glu Arg His Lys Asp Asp Ser Arg Gly Leu Val Leu Pro

35 40 45

Gly Tyr Lys Tyr Leu Gly Pro Phe Asn Gly Leu Asp Lys Gly Glu Pro

50 55 60

Val Asn Glu Ala Asp Ala Ala Ala Leu Glu His Asp Lys Ala Tyr Asp

65 70 75 80

Arg Gln Leu Asp Ser Gly Asp Asn Pro Tyr Leu Lys Tyr Asn His Ala

85 90 95

Asp Ala Glu Phe Gln Glu Arg Leu Lys Glu Asp Thr Ser Phe Gly Gly

100 105 110

Asn Leu Gly Arg Ala Val Phe Gln Ala Lys Lys Arg Ile Leu Glu Pro

115 120 125

Leu Gly Leu Val Glu Glu Pro Val Lys Thr Ala Pro Gly Lys Lys Arg

130 135 140

Pro Val Glu His Ser Pro Ala Glu Pro Asp Ser Ser Ser Gly Thr Gly

145 150 155 160

Lys Ala Gly Gln Gln Pro Ala Arg Lys Arg Leu Asn Phe Gly Gln Thr

165 170 175

Gly Asp Ala Asp Ser Val Pro Asp Pro Gln Pro Leu Gly Gln Pro Pro

180 185 190

Ala Ala Pro Ser Gly Leu Gly Thr Asn Thr Met Ala Ser Gly Ser Gly

195 200 205

Ala Pro Met Ala Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Asn Ser

210 215 220

Ser Gly Asn Trp His Cys Asp Ser Thr Trp Met Gly Asp Arg Val Ile

225 230 235 240

Thr Thr Ser Thr Arg Thr Trp Ala Leu Pro Thr Tyr Asn Asn His Leu

245 250 255

Tyr Lys Gln Ile Ser Ser Gln Ser Gly Ala Ser Asn Asp Asn His Tyr

260 265 270

Phe Gly Tyr Ser Thr Pro Trp Gly Tyr Phe Asp Phe Asn Arg Phe His

275 280 285

Cys His Phe Ser Pro Arg Asp Trp Gln Arg Leu Ile Asn Asn Asn Trp

290 295 300

Gly Phe Arg Pro Lys Arg Leu Ser Phe Lys Leu Phe Asn Ile Gln Val

305 310 315 320

Lys Glu Val Thr Gln Asn Asp Gly Thr Thr Thr Ile Ala Asn Asn Leu

325 330 335

Thr Ser Thr Val Gln Val Phe Thr Asp Ser Glu Tyr Gln Leu Pro Tyr

340 345 350

Val Leu Gly Ser Ala His Gln Gly Cys Leu Pro Pro Phe Pro Ala Asp

355 360 365

Val Phe Met Val Pro Gln Tyr Gly Tyr Leu Thr Leu Asn Asn Gly Ser

370 375 380

Gln Ala Val Gly Arg Ser Ser Phe Tyr Cys Leu Glu Tyr Phe Pro Ser

385 390 395 400

Gln Met Leu Arg Thr Gly Asn Asn Phe Thr Phe Ser Tyr Thr Phe Glu

405 410 415

Asp Val Pro Phe His Ser Ser Tyr Ala His Ser Gln Ser Leu Asp Arg

420 425 430

Leu Met Asn Pro Leu Ile Asp Gln Tyr Leu Tyr Tyr Leu Ser Arg Thr

435 440 445

Asn Thr Pro Ser Gly Thr Thr Thr Met Ser Arg Leu Gln Phe Ser Gln

450 455 460

Ala Gly Ala Ser Asp Ile Arg Asp Gln Ser Arg Asn Trp Leu Pro Gly

465 470 475 480

Pro Cys Tyr Arg Gln Gln Arg Val Ser Lys Thr Ala Ala Asp Asn Asn

485 490 495

Asn Ser Asp Tyr Ser Trp Thr Gly Ala Thr Lys Tyr His Leu Asn Gly

500 505 510

Arg Asp Ser Leu Val Asn Pro Gly Pro Ala Met Ala Ser His Lys Asp

515 520 525

Asp Glu Glu Lys Tyr Phe Pro Gln Ser Gly Val Leu Ile Phe Gly Lys

530 535 540

Gln Asp Ser Gly Lys Thr Asn Val Asp Ile Glu Lys Val Met Ile Thr

545 550 555 560

Asp Glu Glu Glu Ile Arg Thr Thr Asn Pro Val Ala Thr Glu Gln Tyr

565 570 575

Gly Ser Val Ser Thr Asn Leu Gln Ser Gly Asn Thr Gln Ala Ala Thr

580 585 590

Ser Asp Val Asn Thr Gln Gly Val Leu Pro Gly Met Val Trp Gln Asp

595 600 605

Arg Asp Val Tyr Leu Gln Gly Pro Ile Trp Ala Lys Ile Pro His Thr

610 615 620

Asp Gly His Phe His Pro Ser Pro Leu Met Gly Gly Phe Gly Leu Lys

625 630 635 640

His Pro Pro Pro Gln Ile Leu Ile Lys Asn Thr Pro Val Pro Ala Asn

645 650 655

Pro Ser Thr Thr Phe Ser Ala Ala Lys Phe Ala Ser Phe Ile Thr Gln

660 665 670

Tyr Ser Thr Gly Gln Val Ser Val Glu Ile Glu Trp Glu Leu Gln Lys

675 680 685

Glu Asn Ser Lys Arg Trp Asn Pro Glu Ile Gln Tyr Thr Ser Asn Tyr

690 695 700

Asn Lys Ser Val Asn Val Asp Phe Thr Val Asp Thr Asn Gly Val Tyr

705 710 715 720

Ser Glu Pro Arg Pro Ile Gly Thr Arg Tyr Leu Thr Arg Asn Leu

725 730 735

<210> 34

<211> 738

<212> PRT

<213> capsid protein of adeno-associated virus, hu.37

<400> 34

Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser

1 5 10 15

Glu Gly Ile Arg Glu Trp Trp Asp Leu Lys Pro Gly Ala Pro Lys Pro

20 25 30

Lys Ala Asn Gln Gln Lys Gln Asp Asp Gly Arg Gly Leu Val Leu Pro

35 40 45

Gly Tyr Lys Tyr Leu Gly Pro Phe Asn Gly Leu Asp Lys Gly Glu Pro

50 55 60

Val Asn Ala Ala Asp Ala Ala Ala Leu Glu His Asp Lys Ala Tyr Asp

65 70 75 80

Gln Gln Leu Lys Ala Gly Asp Asn Pro Tyr Leu Arg Tyr Asn His Ala

85 90 95

Asp Ala Glu Phe Gln Glu Arg Leu Gln Glu Asp Thr Ser Phe Gly Gly

100 105 110

Asn Leu Gly Arg Ala Val Phe Gln Ala Lys Lys Arg Val Leu Glu Pro

115 120 125

Leu Gly Leu Val Glu Glu Ala Ala Lys Thr Ala Pro Gly Lys Lys Arg

130 135 140

Pro Val Glu Pro Ser Pro Gln Arg Ser Pro Asp Ser Ser Thr Gly Ile

145 150 155 160

Gly Lys Lys Gly Gln Gln Pro Ala Lys Lys Arg Leu Asn Phe Gly Gln

165 170 175

Thr Gly Asp Ser Glu Ser Val Pro Asp Pro Gln Pro Ile Gly Glu Pro

180 185 190

Pro Ala Gly Pro Ser Gly Leu Gly Ser Gly Thr Met Ala Ala Gly Gly

195 200 205

Gly Ala Pro Met Ala Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Ser

210 215 220

Ser Ser Gly Asn Trp His Cys Asp Ser Thr Trp Leu Gly Asp Arg Val

225 230 235 240

Ile Thr Thr Ser Thr Arg Thr Trp Ala Leu Pro Thr Tyr Asn Asn His

245 250 255

Leu Tyr Lys Gln Ile Ser Asn Gly Thr Ser Gly Gly Ser Thr Asn Asp

260 265 270

Asn Thr Tyr Phe Gly Tyr Ser Thr Pro Trp Gly Tyr Phe Asp Phe Asn

275 280 285

Arg Phe His Cys His Phe Ser Pro Arg Asp Trp Gln Arg Leu Ile Asn

290 295 300

Asn Asn Trp Gly Phe Arg Pro Lys Arg Leu Ser Phe Lys Leu Phe Asn

305 310 315 320

Ile Gln Val Lys Glu Val Thr Gln Asn Glu Gly Thr Lys Thr Ile Ala

325 330 335

Asn Asn Leu Thr Ser Thr Ile Gln Val Phe Thr Asp Ser Glu Tyr Gln

340 345 350

Leu Pro Tyr Val Leu Gly Ser Ala His Gln Gly Cys Leu Pro Pro Phe

355 360 365

Pro Ala Asp Val Phe Met Ile Pro Gln Tyr Gly Tyr Leu Thr Leu Asn

370 375 380

Asn Gly Ser Gln Ala Val Gly Arg Ser Ser Phe Tyr Cys Leu Glu Tyr

385 390 395 400

Phe Pro Ser Gln Met Leu Arg Thr Gly Asn Asn Phe Glu Phe Ser Tyr

405 410 415

Thr Phe Glu Asp Val Pro Phe His Ser Ser Tyr Ala His Ser Gln Ser

420 425 430

Leu Asp Arg Leu Met Asn Pro Leu Ile Asp Gln Tyr Leu Tyr Tyr Leu

435 440 445

Ser Arg Thr Gln Ser Thr Gly Gly Thr Gln Gly Thr Gln Gln Leu Leu

450 455 460

Phe Ser Gln Ala Gly Pro Ala Asn Met Ser Ala Gln Ala Lys Asn Trp

465 470 475 480

Leu Pro Gly Pro Cys Tyr Arg Gln Gln Arg Val Ser Thr Thr Leu Ser

485 490 495

Gln Asn Asn Asn Ser Asn Phe Ala Trp Thr Gly Ala Thr Lys Tyr His

500 505 510

Leu Asn Gly Arg Asp Ser Leu Val Asn Pro Gly Val Ala Met Ala Thr

515 520 525

His Lys Asp Asp Glu Glu Arg Phe Phe Pro Ser Ser Gly Val Leu Met

530 535 540

Phe Gly Lys Gln Gly Ala Gly Arg Asp Asn Val Asp Tyr Ser Ser Val

545 550 555 560

Met Leu Thr Ser Glu Glu Glu Ile Lys Thr Thr Asn Pro Val Ala Thr

565 570 575

Glu Gln Tyr Gly Val Val Ala Asp Asn Leu Gln Gln Thr Asn Thr Gly

580 585 590

Pro Ile Val Gly Asn Val Asn Ser Gln Gly Ala Leu Pro Gly Met Val

595 600 605

Trp Gln Asn Arg Asp Val Tyr Leu Gln Gly Pro Ile Trp Ala Lys Ile

610 615 620

Pro His Thr Asp Gly Asn Phe His Pro Ser Pro Leu Met Gly Gly Phe

625 630 635 640

Gly Leu Lys His Pro Pro Pro Gln Ile Leu Ile Lys Asn Thr Pro Val

645 650 655

Pro Ala Asp Pro Pro Thr Thr Phe Ser Gln Ala Lys Leu Ala Ser Phe

660 665 670

Ile Thr Gln Tyr Ser Thr Gly Gln Val Ser Val Glu Ile Glu Trp Glu

675 680 685

Leu Gln Lys Glu Asn Ser Lys Arg Trp Asn Pro Glu Ile Gln Tyr Thr

690 695 700

Ser Asn Tyr Tyr Lys Ser Thr Asn Val Asp Phe Ala Val Asn Thr Glu

705 710 715 720

Gly Thr Tyr Ser Glu Pro Arg Pro Ile Gly Thr Arg Tyr Leu Thr Arg

725 730 735

Asn Leu

<210> 35

<211> 734

<212> PRT

<213> capsid protein of adeno-associated virus, hu.53

<400> 35

Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Thr Leu Ser

1 5 10 15

Glu Gly Ile Arg Gln Trp Trp Lys Leu Lys Pro Gly Pro Pro Pro Pro

20 25 30

Lys Pro Ala Glu Arg His Lys Asp Asp Ser Arg Gly Leu Val Leu Pro

35 40 45

Gly Tyr Lys Tyr Leu Gly Pro Phe Asn Gly Leu Asp Lys Gly Glu Pro

50 55 60

Val Asn Glu Ala Asp Ala Ala Ala Leu Glu His Asp Lys Ala Tyr Asp

65 70 75 80

Arg Gln Leu Asp Ser Gly Asp Asn Pro Tyr Leu Lys Tyr Asn His Ala

85 90 95

Asp Ala Glu Phe Gln Glu Arg Leu Lys Glu Asp Thr Ser Phe Gly Gly

100 105 110

Asn Leu Gly Arg Ala Val Phe Gln Ala Lys Lys Arg Val Leu Glu Pro

115 120 125

Leu Gly Leu Val Glu Glu Pro Val Lys Thr Ala Pro Gly Lys Lys Arg

130 135 140

Pro Val Glu His Ser Pro Ala Glu Pro Asp Ser Ser Ser Gly Thr Gly

145 150 155 160

Lys Ala Gly Gln Gln Pro Ala Arg Lys Arg Leu Asn Phe Gly Gln Thr

165 170 175

Gly Asp Ala Asp Ser Val Pro Asp Pro Gln Pro Leu Arg Gln Pro Pro

180 185 190

Ala Ala Pro Thr Ser Leu Gly Ser Thr Thr Met Ala Thr Gly Ser Gly

195 200 205

Ala Pro Met Ala Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Asn Ser

210 215 220

Ser Gly Asn Trp His Cys Asp Ser Gln Trp Leu Gly Asp Arg Val Ile

225 230 235 240

Thr Thr Ser Thr Arg Thr Trp Ala Leu Pro Thr Tyr Asn Asn His Leu

245 250 255

Tyr Lys Gln Ile Ser Ser Gln Ser Gly Ala Ser Asn Asp Asn His Tyr

260 265 270

Phe Gly Tyr Ser Thr Pro Trp Gly Tyr Phe Asp Phe Asn Arg Phe His

275 280 285

Cys His Phe Ser Pro Arg Asp Trp Gln Arg Leu Ile Asn Asn Asn Trp

290 295 300

Gly Phe Arg Pro Lys Arg Leu Asn Phe Lys Leu Phe Asn Ile Gln Val

305 310 315 320

Lys Glu Val Thr Gln Asn Asp Gly Thr Thr Thr Ile Ala Asn Asn Leu

325 330 335

Thr Ser Thr Val Gln Val Phe Thr Asp Ser Glu Tyr Gln Leu Pro Tyr

340 345 350

Val Leu Gly Ser Ala His Gln Gly Cys Leu Pro Pro Phe Pro Ala Asp

355 360 365

Val Phe Met Val Pro Gln Tyr Gly Tyr Leu Thr Leu Asn Asn Gly Ser

370 375 380

Gln Ala Val Gly Arg Ser Ser Phe Tyr Cys Leu Glu Tyr Phe Pro Ser

385 390 395 400

Gln Met Leu Arg Thr Gly Asn Asn Phe Gln Phe Ser Tyr Thr Phe Glu

405 410 415

Asp Val Pro Phe His Ser Ser Tyr Ala His Ser Gln Ser Leu Asp Arg

420 425 430

Leu Met Asn Pro Leu Ile Asp Gln Tyr Leu Tyr Tyr Leu Asn Arg Thr

435 440 445

Gln Thr Ala Ser Gly Thr Gln Gln Ser Arg Leu Leu Phe Ser Gln Ala

450 455 460

Gly Pro Thr Ser Met Ser Leu Gln Ala Lys Asn Trp Leu Pro Gly Pro

465 470 475 480

Cys Tyr Arg Gln Gln Arg Leu Ser Lys Gln Ala Asn Asp Asn Asn Asn

485 490 495

Ser Asn Phe Pro Trp Thr Gly Ala Thr Lys Tyr Tyr Leu Asn Gly Arg

500 505 510

Asp Ser Leu Val Asn Pro Gly Pro Ala Met Ala Ser His Lys Asp Asp

515 520 525

Glu Glu Lys Phe Phe Pro Met His Gly Thr Leu Ile Phe Gly Lys Glu

530 535 540

Gly Thr Asn Ala Thr Asn Ala Glu Leu Glu Asn Val Met Ile Thr Asp

545 550 555 560

Glu Glu Glu Ile Arg Thr Thr Asn Pro Val Ala Thr Glu Gln Tyr Gly

565 570 575

Tyr Val Ser Asn Asn Leu Gln Asn Ser Asn Thr Ala Ala Ser Thr Glu

580 585 590

Thr Val Asn His Gln Gly Ala Leu Pro Gly Met Val Trp Gln Asp Arg

595 600 605

Asp Val Tyr Leu Gln Gly Pro Ile Trp Ala Lys Ile Pro His Thr Asp

610 615 620

Gly His Phe His Pro Ser Pro Leu Met Gly Gly Phe Gly Leu Lys His

625 630 635 640

Pro Pro Pro Gln Ile Met Ile Lys Asn Thr Pro Val Pro Ala Asn Pro

645 650 655

Pro Thr Asn Phe Ser Ser Ala Lys Phe Ala Ser Phe Ile Thr Gln Tyr

660 665 670

Ser Thr Gly Gln Val Ser Val Glu Ile Glu Trp Glu Leu Gln Lys Glu

675 680 685

Asn Ser Lys Arg Trp Asn Pro Glu Ile Gln Tyr Thr Ser Asn Tyr Asn

690 695 700

Lys Ser Val Asn Val Asp Phe Thr Val Asp Thr Asn Gly Val Tyr Ser

705 710 715 720

Glu Pro Arg Pro Ile Gly Thr Arg Tyr Leu Thr Arg Asn Leu

725 730

<210> 36

<211> 738

<212> PRT

<213> capsid protein of macaque gland-associated virus, rh.39

<400> 36

Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser

1 5 10 15

Glu Gly Ile Arg Glu Trp Trp Asp Leu Lys Pro Gly Ala Pro Lys Pro

20 25 30

Lys Ala Asn Gln Gln Lys Gln Asp Asp Gly Arg Gly Leu Val Leu Pro

35 40 45

Gly Tyr Lys Tyr Leu Gly Pro Phe Asn Gly Leu Asp Lys Gly Glu Pro

50 55 60

Val Asn Ala Ala Asp Ala Ala Ala Leu Glu His Asp Lys Ala Tyr Asp

65 70 75 80

Gln Gln Leu Lys Ala Gly Asp Asn Pro Tyr Leu Arg Tyr Asn His Ala

85 90 95

Asp Ala Glu Phe Gln Glu Arg Leu Gln Glu Asp Thr Ser Phe Gly Gly

100 105 110

Asn Leu Gly Arg Ala Val Phe Gln Ala Lys Lys Arg Val Leu Glu Pro

115 120 125

Leu Gly Leu Val Glu Glu Ala Ala Lys Thr Ala Pro Gly Lys Lys Arg

130 135 140

Pro Val Glu Pro Ser Pro Gln Arg Ser Pro Asp Ser Ser Thr Gly Ile

145 150 155 160

Gly Lys Lys Gly Gln Gln Pro Ala Lys Lys Arg Leu Asn Phe Gly Gln

165 170 175

Thr Gly Asp Ser Glu Ser Val Pro Asp Pro Gln Pro Ile Gly Glu Pro

180 185 190

Pro Ala Gly Pro Ser Gly Leu Gly Ser Gly Thr Met Ala Ala Gly Gly

195 200 205

Gly Ala Pro Met Ala Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Ser

210 215 220

Ser Ser Gly Asn Trp His Cys Asp Ser Thr Trp Leu Gly Asp Arg Val

225 230 235 240

Ile Thr Thr Ser Thr Arg Thr Trp Ala Leu Pro Thr Tyr Asn Asn His

245 250 255

Leu Tyr Lys Gln Ile Ser Asn Gly Thr Ser Gly Gly Ser Thr Asn Asp

260 265 270

Asn Thr Tyr Phe Gly Tyr Ser Thr Pro Trp Gly Tyr Phe Asp Phe Asn

275 280 285

Arg Phe His Cys His Phe Ser Pro Arg Asp Trp Gln Arg Leu Ile Asn

290 295 300

Asn Asn Trp Gly Phe Arg Pro Lys Arg Leu Ser Phe Lys Leu Phe Asn

305 310 315 320

Ile Gln Val Lys Glu Val Thr Gln Asn Glu Gly Thr Lys Thr Ile Ala

325 330 335

Asn Asn Leu Thr Ser Thr Ile Gln Val Phe Thr Asp Ser Glu Tyr Gln

340 345 350

Leu Pro Tyr Val Leu Gly Ser Ala His Gln Gly Cys Leu Pro Pro Phe

355 360 365

Pro Ala Asp Val Phe Met Ile Pro Gln Tyr Gly Tyr Leu Thr Leu Asn

370 375 380

Asn Gly Ser Gln Ala Val Gly Arg Ser Ser Phe Tyr Cys Leu Glu Tyr

385 390 395 400

Phe Pro Ser Gln Met Leu Arg Thr Gly Asn Asn Phe Glu Phe Ser Tyr

405 410 415

Thr Phe Glu Asp Val Pro Phe His Ser Ser Tyr Ala His Ser Gln Ser

420 425 430

Leu Asp Arg Leu Met Asn Pro Leu Ile Asp Gln Tyr Leu Tyr Tyr Leu

435 440 445

Ser Arg Thr Gln Ser Thr Gly Gly Thr Gln Gly Thr Gln Gln Leu Leu

450 455 460

Phe Ser Gln Ala Gly Pro Ala Asn Met Ser Ala Gln Ala Lys Asn Trp

465 470 475 480

Leu Pro Gly Pro Cys Tyr Arg Gln Gln Arg Val Ser Thr Thr Leu Ser

485 490 495

Gln Asn Asn Asn Ser Asn Phe Ala Trp Thr Gly Ala Thr Lys Tyr His

500 505 510

Leu Asn Gly Arg Asp Ser Leu Val Asn Pro Gly Val Ala Met Ala Thr

515 520 525

His Lys Asp Asp Glu Glu Arg Phe Phe Pro Ser Ser Gly Val Leu Met

530 535 540

Phe Gly Lys Gln Gly Ala Gly Arg Asp Asn Val Asp Tyr Ser Ser Val

545 550 555 560

Met Leu Thr Ser Glu Glu Glu Ile Lys Thr Thr Asn Pro Val Ala Thr

565 570 575

Glu Gln Tyr Gly Val Val Ala Asp Asn Leu Gln Gln Thr Asn Thr Gly

580 585 590

Pro Ile Val Gly Asn Val Asn Ser Gln Gly Ala Leu Pro Gly Met Val

595 600 605

Trp Gln Asn Arg Asp Val Tyr Leu Gln Gly Pro Ile Trp Ala Lys Ile

610 615 620

Pro His Thr Asp Gly Asn Phe His Pro Ser Pro Leu Met Gly Gly Phe

625 630 635 640

Gly Leu Lys His Pro Pro Pro Gln Ile Leu Ile Lys Asn Thr Pro Val

645 650 655

Pro Ala Asp Pro Pro Thr Thr Phe Ser Gln Ala Lys Leu Ala Ser Phe

660 665 670

Ile Thr Gln Tyr Ser Thr Gly Gln Val Ser Val Glu Ile Glu Trp Glu

675 680 685

Leu Gln Lys Glu Asn Ser Lys Arg Trp Asn Pro Glu Ile Gln Tyr Thr

690 695 700

Ser Asn Tyr Tyr Lys Ser Thr Asn Val Asp Phe Ala Val Asn Thr Glu

705 710 715 720

Gly Thr Tyr Ser Glu Pro Arg Pro Ile Gly Thr Arg Tyr Leu Thr Arg

725 730 735

Asn Leu

<210> 37

<211> 736

<212> PRT

<213> capsid protein of macaque gland-associated virus, rh.43

<400> 37

Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser

1 5 10 15

Glu Gly Ile Arg Glu Trp Trp Asp Leu Lys Pro Gly Ala Pro Lys Pro

20 25 30

Lys Ala Asn Gln Gln Lys Gln Asp Asp Gly Arg Gly Leu Val Leu Pro

35 40 45

Gly Tyr Lys Tyr Leu Gly Pro Phe Asn Gly Leu Asp Lys Gly Glu Pro

50 55 60

Val Asn Ala Ala Asp Ala Ala Ala Leu Glu His Asp Lys Ala Tyr Asp

65 70 75 80

Gln Gln Leu Glu Ala Gly Asp Asn Pro Tyr Leu Arg Tyr Asn His Ala

85 90 95

Asp Ala Glu Phe Gln Glu Arg Leu Gln Glu Asp Thr Ser Phe Gly Gly

100 105 110

Asn Leu Gly Arg Ala Val Phe Gln Ala Lys Lys Arg Val Leu Glu Pro

115 120 125

Leu Gly Leu Val Glu Glu Gly Ala Lys Thr Ala Pro Gly Lys Lys Arg

130 135 140

Pro Val Glu Gln Ser Pro Gln Glu Pro Asp Ser Ser Ser Gly Ile Gly

145 150 155 160

Lys Lys Gly Gln Gln Pro Ala Arg Lys Arg Leu Asn Phe Gly Gln Thr

165 170 175

Gly Asp Ser Glu Ser Val Pro Asp Pro Gln Pro Leu Gly Glu Pro Pro

180 185 190

Ala Ala Pro Ser Gly Val Gly Pro Asn Thr Met Ala Ala Gly Gly Gly

195 200 205

Ala Pro Met Ala Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Ser Ser

210 215 220

Ser Gly Asn Trp His Cys Asp Ser Thr Trp Leu Gly Asp Arg Val Ile

225 230 235 240

Thr Thr Ser Thr Arg Thr Trp Ala Leu Pro Thr Tyr Asn Asn His Leu

245 250 255

Tyr Lys Gln Ile Ser Asn Gly Thr Ser Gly Gly Ala Thr Asn Asp Asn

260 265 270

Thr Tyr Phe Gly Tyr Ser Thr Pro Trp Gly Tyr Phe Asp Phe Asn Arg

275 280 285

Phe His Cys His Phe Ser Pro Arg Asp Trp Gln Arg Leu Ile Asn Asn

290 295 300

Asn Trp Gly Phe Arg Pro Lys Arg Leu Ser Phe Lys Leu Phe Asn Ile

305 310 315 320

Gln Val Lys Glu Val Thr Gln Asn Glu Gly Thr Lys Thr Ile Ala Asn

325 330 335

Asn Leu Thr Ser Thr Ile Gln Val Phe Thr Asp Ser Glu Tyr Gln Leu

340 345 350

Pro Tyr Val Leu Gly Ser Ala His Gln Gly Cys Leu Pro Pro Phe Pro

355 360 365

Ala Asp Val Phe Met Ile Pro Gln Tyr Gly Tyr Leu Thr Leu Asn Asn

370 375 380

Gly Ser Gln Ala Val Gly Arg Ser Ser Phe Tyr Cys Leu Glu Tyr Phe

385 390 395 400

Pro Ser Gln Met Leu Arg Thr Gly Asn Asn Phe Gln Phe Thr Tyr Thr

405 410 415

Phe Glu Asp Val Pro Phe His Ser Ser Tyr Ala His Ser Gln Ser Leu

420 425 430

Asp Arg Leu Met Asn Pro Leu Ile Asp Gln Tyr Leu Tyr Tyr Leu Ser

435 440 445

Arg Thr Gln Thr Thr Gly Gly Thr Ala Asn Thr Gln Thr Leu Gly Phe

450 455 460

Ser Gln Gly Gly Pro Asn Thr Met Ala Asn Gln Ala Lys Asn Trp Leu

465 470 475 480

Pro Gly Pro Cys Tyr Arg Gln Gln Arg Val Ser Thr Thr Thr Gly Gln

485 490 495

Asn Asn Asn Ser Asn Phe Ala Trp Thr Ala Gly Thr Lys Tyr His Leu

500 505 510

Asn Gly Arg Asn Ser Leu Ala Asn Pro Gly Ile Ala Met Ala Thr His

515 520 525

Lys Asp Asp Glu Glu Arg Phe Phe Pro Val Thr Gly Ser Cys Phe Trp

530 535 540

Gln Gln Asn Ala Ala Arg Asp Asn Ala Asp Tyr Ser Asp Val Met Leu

545 550 555 560

Thr Ser Glu Glu Glu Ile Lys Thr Thr Asn Pro Val Ala Thr Glu Glu

565 570 575

Tyr Gly Ile Val Ala Asp Asn Leu Gln Gln Gln Asn Thr Ala Pro Gln

580 585 590

Ile Gly Thr Val Asn Ser Gln Gly Ala Leu Pro Gly Met Val Trp Gln

595 600 605

Asn Arg Asp Val Tyr Leu Gln Gly Pro Ile Trp Ala Lys Ile Pro His

610 615 620

Thr Asp Gly Asn Phe His Pro Ser Pro Leu Met Gly Gly Phe Gly Leu

625 630 635 640

Lys His Pro Pro Pro Gln Ile Leu Ile Lys Asn Thr Pro Val Pro Ala

645 650 655

Asp Pro Pro Thr Thr Phe Asn Gln Ser Lys Leu Asn Ser Phe Ile Thr

660 665 670

Gln Tyr Ser Thr Gly Gln Val Ser Val Glu Ile Glu Trp Glu Leu Gln

675 680 685

Lys Glu Asn Ser Lys Arg Trp Asn Pro Glu Ile Gln Tyr Thr Ser Asn

690 695 700

Tyr Tyr Lys Ser Thr Ser Val Asp Phe Ala Val Asn Thr Glu Gly Val

705 710 715 720

Tyr Ser Glu Pro Arg Pro Ile Gly Thr Arg Tyr Leu Thr Arg Asn Leu

725 730 735

<210> 38

<211> 738

<212> PRT

<213> capsid protein of macaque gland-associated virus, rh.46

<400> 38

Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser

1 5 10 15

Glu Gly Ile Arg Glu Trp Trp Asp Leu Lys Pro Gly Ala Pro Lys Pro

20 25 30

Lys Ala Asn Gln Gln Lys Gln Asp Asp Gly Arg Gly Leu Val Leu Pro

35 40 45

Gly Tyr Lys Tyr Leu Gly Pro Phe Asn Gly Leu Asp Lys Gly Glu Pro

50 55 60

Val Asn Ala Ala Asp Ala Ala Ala Leu Glu His Asp Lys Ala Tyr Asp

65 70 75 80

Gln Gln Leu Lys Ala Gly Asp Asn Pro Tyr Leu Arg Tyr Asn His Ala

85 90 95

Asp Ala Glu Phe Gln Glu Arg Leu Gln Glu Asp Thr Ser Phe Gly Gly

100 105 110

Asn Leu Gly Arg Ala Val Phe Gln Ala Lys Lys Arg Val Leu Glu Pro

115 120 125

Leu Gly Leu Val Glu Glu Gly Ala Lys Thr Ala Pro Gly Lys Lys Arg

130 135 140

Pro Val Glu Pro Ser Pro Gln Arg Ser Pro Asp Ser Ser Thr Gly Ile

145 150 155 160

Gly Lys Lys Gly Gln Gln Pro Ala Arg Lys Arg Leu Asn Phe Gly Gln

165 170 175

Thr Gly Asp Ser Glu Ser Val Pro Asp Pro Gln Pro Ile Gly Glu Pro

180 185 190

Pro Ala Ala Pro Ser Ser Val Gly Ser Gly Thr Met Ala Ala Gly Gly

195 200 205

Gly Ala Pro Met Ala Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Ser

210 215 220

Ser Ser Gly Asn Trp His Cys Asp Ser Thr Trp Leu Gly Asp Arg Val

225 230 235 240

Ile Thr Thr Ser Thr Arg Thr Trp Ala Leu Pro Thr Tyr Asn Asn His

245 250 255

Leu Tyr Lys Gln Ile Ser Asn Gly Thr Ser Gly Gly Ser Thr Asn Asp

260 265 270

Asn Thr Tyr Phe Gly Tyr Ser Thr Pro Trp Gly Tyr Phe Asp Phe Asn

275 280 285

Arg Phe His Cys His Phe Ser Pro Arg Asp Trp Gln Arg Leu Ile Asn

290 295 300

Asn Asn Trp Gly Phe Arg Pro Lys Arg Leu Ser Phe Lys Leu Phe Asn

305 310 315 320

Ile Gln Val Lys Glu Val Thr Gln Asn Glu Gly Thr Lys Thr Ile Ala

325 330 335

Asn Asn Leu Thr Ser Thr Ile Gln Val Phe Thr Asp Ser Glu Tyr Gln

340 345 350

Leu Pro Tyr Val Leu Gly Ser Ala His Gln Gly Cys Leu Pro Pro Phe

355 360 365

Pro Ala Asp Val Phe Met Ile Pro Gln Tyr Gly Tyr Leu Thr Leu Asn

370 375 380

Asn Gly Ser Gln Ala Val Gly Arg Ser Ser Phe Tyr Cys Leu Glu Tyr

385 390 395 400

Phe Pro Ser Gln Met Leu Arg Thr Gly Asn Asn Phe Ser Phe Ser Tyr

405 410 415

Thr Phe Glu Asp Val Pro Phe His Ser Ser Tyr Ala His Ser Gln Ser

420 425 430

Leu Asp Arg Leu Met Asn Pro Leu Ile Asp Gln Tyr Leu Tyr Tyr Leu

435 440 445

Ser Arg Thr Gln Ser Thr Gly Gly Thr Ala Gly Thr Gln Gln Leu Leu

450 455 460

Phe Ser Gln Ala Gly Pro Ser Asn Met Ser Ala Gln Ala Arg Asn Trp

465 470 475 480

Leu Pro Gly Pro Cys Tyr Arg Gln Gln Arg Val Ser Thr Thr Leu Ser

485 490 495

Gln Asn Asn Asn Ser Asn Phe Ala Trp Thr Gly Ala Thr Lys Tyr His

500 505 510

Leu Asn Gly Arg Asp Ser Leu Val Asn Pro Gly Val Ala Met Ala Thr

515 520 525

Asn Lys Asp Asp Glu Asp Arg Phe Phe Pro Ser Ser Gly Ile Leu Met

530 535 540

Phe Gly Lys Gln Gly Ala Gly Lys Asp Asn Val Asp Tyr Ser Asn Val

545 550 555 560

Met Leu Thr Ser Glu Glu Glu Ile Lys Ala Thr Asn Pro Val Ala Thr

565 570 575

Glu Gln Tyr Gly Val Val Ala Asp Asn Leu Gln Gln Gln Asn Thr Ala

580 585 590

Pro Ile Val Gly Ala Val Asn Ser Gln Gly Ala Leu Pro Gly Met Val

595 600 605

Trp Gln Asn Arg Asp Val Tyr Leu Gln Gly Pro Ile Trp Ala Lys Ile

610 615 620

Pro His Thr Asp Gly Asn Phe His Pro Ser Pro Leu Met Gly Gly Phe

625 630 635 640

Gly Leu Lys His Pro Pro Pro Gln Ile Leu Ile Lys Asn Thr Pro Val

645 650 655

Pro Ala Asp Pro Pro Thr Ala Phe Asn Gln Ala Lys Leu Asn Ser Phe

660 665 670

Ile Thr Gln Tyr Ser Thr Gly Gln Val Ser Val Glu Ile Glu Trp Glu

675 680 685

Leu Gln Lys Glu Asn Ser Lys Arg Trp Asn Pro Glu Ile Gln Tyr Thr

690 695 700

Ser Asn Tyr Tyr Lys Ser Thr Asn Val Asp Phe Ala Val Asn Thr Glu

705 710 715 720

Gly Val Tyr Ser Glu Pro Arg Pro Ile Gly Thr Arg Tyr Leu Thr Arg

725 730 735

Asn Leu

<210> 39

<211> 738

<212> PRT

<213> capsid protein of macaque gland-associated virus, rh.2

<400> 39

Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser

1 5 10 15

Glu Gly Ile Arg Glu Trp Trp Asp Leu Lys Pro Gly Ala Pro Lys Pro

20 25 30

Lys Ala Asn Gln Gln Lys Gln Asp Asp Gly Arg Gly Leu Val Leu Pro

35 40 45

Gly Tyr Lys Tyr Leu Gly Pro Phe Asn Gly Leu Asp Lys Gly Glu Pro

50 55 60

Val Asn Ala Ala Asp Ala Ala Ala Leu Glu His Asp Lys Ala Tyr Asp

65 70 75 80

Gln Gln Leu Lys Ala Gly Asp Asn Pro Tyr Leu Arg Tyr Asn His Ala

85 90 95

Asp Ala Glu Phe Gln Glu Arg Leu Gln Glu Asp Thr Ser Phe Gly Gly

100 105 110

Asn Leu Gly Arg Ala Val Phe Gln Ala Lys Lys Arg Val Leu Glu Pro

115 120 125

Leu Gly Leu Val Glu Glu Gly Ala Lys Thr Ala Pro Gly Lys Lys Arg

130 135 140

Pro Val Glu Pro Ser Pro Gln Arg Ser Pro Asp Ser Ser Thr Gly Ile

145 150 155 160

Gly Lys Lys Gly His Gln Pro Ala Arg Lys Arg Leu Asn Phe Gly Gln

165 170 175

Thr Gly Asp Ser Glu Ser Val Pro Asp Pro Gln Pro Ile Gly Glu Pro

180 185 190

Pro Ala Gly Pro Ser Gly Leu Gly Ser Gly Thr Met Ala Ala Gly Gly

195 200 205

Gly Ala Pro Met Ala Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Ser

210 215 220

Ser Ser Gly Asn Trp His Cys Asp Ser Thr Trp Leu Gly Asp Arg Val

225 230 235 240

Ile Thr Thr Ser Thr Arg Thr Trp Ala Leu Pro Thr Tyr Asn Asn His

245 250 255

Leu Tyr Lys Gln Ile Ser Asn Gly Thr Ser Gly Gly Ser Thr Asn Asp

260 265 270

Asn Thr Tyr Phe Gly Tyr Ser Thr Pro Trp Gly Tyr Phe Asp Phe Asn

275 280 285

Arg Phe His Cys His Phe Ser Pro Arg Asp Trp Gln Arg Leu Ile Asn

290 295 300

Asn Asn Trp Gly Phe Arg Pro Lys Arg Leu Asn Phe Lys Leu Phe Asn

305 310 315 320

Ile Gln Val Lys Glu Val Thr Gln Asn Glu Gly Thr Lys Thr Ile Ala

325 330 335

Asn Asn Leu Thr Ser Thr Ile Gln Val Phe Thr Asp Ser Glu Tyr Gln

340 345 350

Leu Pro Tyr Val Pro Gly Ser Ala His Gln Gly Cys Leu Pro Pro Phe

355 360 365

Pro Ala Asp Val Phe Met Ile Pro Gln Tyr Gly Tyr Leu Thr Leu Asn

370 375 380

Asn Gly Ser Gln Ala Val Gly Arg Ser Ser Phe Tyr Cys Leu Glu Tyr

385 390 395 400

Phe Pro Ser Gln Met Leu Arg Thr Gly Asn Asn Phe Glu Phe Ser Tyr

405 410 415

Thr Phe Glu Asp Val Pro Phe His Ser Ser Tyr Ala His Ser Gln Ser

420 425 430

Leu Asp Arg Leu Met Asn Pro Leu Ile Asp Gln Tyr Leu Tyr Tyr Leu

435 440 445

Ser Arg Thr Gln Ser Thr Gly Gly Thr Gln Gly Thr Gln Gln Leu Leu

450 455 460

Phe Ser Gln Ala Gly Pro Ala Asn Met Ser Ala Gln Ala Lys Asn Trp

465 470 475 480

Leu Pro Gly Pro Cys Tyr Arg Gln Gln Arg Val Ser Thr Thr Leu Ser

485 490 495

Gln Asn Asn Asn Ser Asn Phe Ala Trp Thr Gly Ala Thr Lys Tyr His

500 505 510

Leu Asn Gly Arg Asp Ser Leu Val Asn Pro Gly Val Ala Met Ala Thr

515 520 525

His Lys Asp Asp Glu Glu Arg Phe Phe Pro Ser Ser Gly Val Leu Met

530 535 540

Phe Gly Lys Gln Gly Ala Gly Lys Asp Asn Val Asp Tyr Ser Ser Val

545 550 555 560

Met Leu Thr Ser Glu Glu Glu Ile Lys Thr Thr Asn Pro Val Ala Thr

565 570 575

Glu Gln Tyr Gly Val Val Ala Asp Asn Leu Gln Gln Thr Asn Gly Ala

580 585 590

Pro Ile Val Gly Thr Val Asn Ser Gln Gly Ala Leu Pro Gly Met Val

595 600 605

Trp Gln Asn Arg Asp Val Tyr Leu Gln Gly Pro Ile Trp Ala Lys Ile

610 615 620

Pro His Thr Asp Gly Asn Phe His Pro Ser Pro Leu Met Gly Gly Phe

625 630 635 640

Gly Leu Lys His Pro Pro Pro Gln Ile Leu Val Lys Asn Thr Pro Val

645 650 655

Pro Ala Asp Pro Pro Thr Thr Phe Ser Gln Ala Lys Leu Ala Ser Phe

660 665 670

Ile Thr Gln Tyr Ser Thr Gly Gln Val Ser Val Glu Ile Glu Trp Glu

675 680 685

Leu Gln Lys Glu Asn Ser Lys Arg Trp Asn Pro Glu Ile Gln Tyr Thr

690 695 700

Ser Asn Tyr Tyr Lys Ser Thr Asn Val Asp Phe Ala Val Asn Thr Glu

705 710 715 720

Gly Thr Tyr Ser Glu Pro Arg Pro Ile Gly Thr Arg Tyr Leu Thr Arg

725 730 735

Asn Leu

<210> 40

<211> 729

<212> PRT

<213> capsid protein of macaque gland-associated virus, rh.37

<400> 40

Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser

1 5 10 15

Glu Gly Ile Arg Glu Trp Trp Asp Leu Lys Pro Gly Ala Pro Lys Pro

20 25 30

Lys Ala Asn Gln Gln Lys Gln Asp Asp Gly Arg Gly Leu Val Leu Pro

35 40 45

Gly Tyr Lys Tyr Leu Gly Pro Phe Asn Gly Leu Asp Lys Gly Glu Pro

50 55 60

Val Asn Ala Ala Asp Ala Ala Ala Leu Glu His Asp Lys Ala Tyr Asp

65 70 75 80

Gln Gln Leu Lys Ala Gly Asp Asn Pro Tyr Leu Arg Tyr Asn His Ala

85 90 95

Asp Ala Glu Phe Gln Glu Arg Leu Gln Glu Asp Thr Ser Phe Gly Gly

100 105 110

Asn Leu Gly Arg Ala Val Phe Gln Ala Lys Lys Arg Val Leu Glu Pro

115 120 125

Leu Gly Leu Val Glu Glu Gly Ala Lys Thr Ala Pro Gly Lys Lys Arg

130 135 140

Pro Ile Asp Ser Pro Asp Ser Ser Thr Gly Ile Gly Lys Lys Gly Gln

145 150 155 160

Gln Pro Ala Lys Lys Lys Leu Asn Phe Gly Gln Thr Gly Asp Ser Glu

165 170 175

Ser Val Pro Asp Pro Gln Pro Leu Gly Glu Pro Pro Ala Ala Pro Ser

180 185 190

Ser Val Gly Ser Gly Thr Met Ala Ala Gly Gly Gly Ala Pro Thr Ala

195 200 205

Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Asn Ala Ser Gly Asn Trp

210 215 220

His Cys Asp Ser Thr Trp Leu Gly Asp Arg Val Ile Thr Thr Ser Thr

225 230 235 240

Arg Thr Trp Ala Leu Pro Thr Tyr Asn Asn His Leu Tyr Lys Gln Ile

245 250 255

Ser Ser Ser Ser Ser Gly Ala Thr Asn Asp Asn His Tyr Phe Gly Tyr

260 265 270

Ser Thr Pro Trp Gly Tyr Phe Asp Phe Asn Arg Phe His Cys His Phe

275 280 285

Ser Pro Arg Asp Trp Gln Arg Leu Ile Asn Asn Asn Trp Gly Phe Arg

290 295 300

Pro Lys Lys Leu Arg Phe Lys Leu Phe Asn Ile Gln Val Lys Glu Val

305 310 315 320

Thr Thr Asn Asp Gly Val Thr Thr Ile Ala Asn Asn Leu Thr Ser Thr

325 330 335

Val Gln Val Phe Ser Asp Ser Glu Tyr Gln Leu Pro Tyr Val Leu Gly

340 345 350

Ser Ala His Gln Gly Cys Leu Pro Pro Phe Pro Ala Asp Val Phe Met

355 360 365

Ile Pro Gln Tyr Gly Tyr Leu Thr Leu Asn Asn Gly Ser Gln Ser Val

370 375 380

Gly Arg Ser Ser Phe Tyr Cys Leu Glu Tyr Phe Pro Ser Gln Met Leu

385 390 395 400

Arg Thr Gly Asn Asn Phe Glu Phe Ser Tyr Ser Phe Glu Asp Val Pro

405 410 415

Phe His Ser Ser Tyr Ala His Ser Gln Ser Leu Asp Arg Leu Met Asn

420 425 430

Pro Leu Ile Asp Gln Tyr Leu Tyr Tyr Leu Ala Arg Thr Gln Ser Thr

435 440 445

Thr Gly Ser Thr Arg Glu Leu Gln Phe His Gln Ala Gly Pro Asn Thr

450 455 460

Met Ala Glu Gln Ser Lys Asn Trp Leu Pro Gly Pro Cys Tyr Arg Gln

465 470 475 480

Gln Arg Leu Ser Lys Asn Leu Asp Phe Asn Asn Asn Ser Asn Phe Ala

485 490 495

Trp Thr Ala Ala Thr Lys Tyr His Leu Asn Gly Arg Asn Ser Leu Thr

500 505 510

Asn Pro Gly Ile Pro Met Ala Thr Asn Lys Asp Asp Glu Asp Gln Phe

515 520 525

Phe Pro Ile Asn Gly Val Leu Val Phe Gly Lys Thr Gly Ala Ala Asn

530 535 540

Lys Thr Thr Leu Glu Asn Val Leu Met Thr Ser Glu Glu Glu Ile Lys

545 550 555 560

Thr Thr Asn Pro Val Ala Thr Glu Glu Tyr Gly Val Val Ser Ser Asn

565 570 575

Leu Gln Ser Ser Thr Ala Gly Pro Gln Ser Gln Thr Ile Asn Ser Gln

580 585 590

Gly Ala Leu Pro Gly Met Val Trp Gln Asn Arg Asp Val Tyr Leu Gln

595 600 605

Gly Pro Ile Trp Ala Lys Ile Pro His Thr Asp Gly Asn Phe His Pro

610 615 620

Ser Pro Leu Met Gly Gly Phe Gly Leu Glu His Pro Pro Pro Gln Ile

625 630 635 640

Leu Ile Lys Asn Thr Pro Val Pro Ala Asn Pro Pro Glu Val Phe Thr

645 650 655

Pro Ala Lys Phe Ala Ser Phe Ile Thr Gln Tyr Ser Thr Gly Gln Val

660 665 670

Ser Val Glu Ile Glu Trp Glu Leu Gln Lys Glu Asn Ser Lys Arg Trp

675 680 685

Asn Pro Glu Ile Gln Tyr Thr Ser Asn Tyr Ala Lys Ser Asn Asn Val

690 695 700

Glu Phe Ala Val Asn Pro Asp Gly Val Tyr Thr Glu Pro Arg Pro Ile

705 710 715 720

Gly Thr Arg Tyr Leu Thr Arg Asn Leu

725

<210> 41

<211> 736

<212> PRT

<213> capsid protein of macaque gland-associated virus, rh.8

<400> 41

Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser

1 5 10 15

Glu Gly Ile Arg Glu Trp Trp Asp Leu Lys Pro Gly Ala Pro Lys Pro

20 25 30

Lys Ala Asn Gln Gln Lys Gln Asp Asp Gly Arg Gly Leu Val Leu Pro

35 40 45

Gly Tyr Lys Tyr Leu Gly Pro Phe Asn Gly Leu Asp Lys Gly Glu Pro

50 55 60

Val Asn Ala Ala Asp Ala Ala Ala Leu Glu His Asp Lys Ala Tyr Asp

65 70 75 80

Gln Gln Leu Lys Ala Gly Asp Asn Pro Tyr Leu Arg Tyr Asn His Ala

85 90 95

Asp Ala Glu Phe Gln Glu Arg Leu Gln Glu Asp Thr Ser Phe Gly Gly

100 105 110

Asn Leu Gly Arg Ala Val Phe Gln Ala Lys Lys Arg Val Leu Glu Pro

115 120 125

Leu Gly Leu Val Glu Glu Gly Ala Lys Thr Ala Pro Gly Lys Lys Arg

130 135 140

Pro Val Glu Gln Ser Pro Gln Glu Pro Asp Ser Ser Ser Gly Ile Gly

145 150 155 160

Lys Thr Gly Gln Gln Pro Ala Lys Lys Arg Leu Asn Phe Gly Gln Thr

165 170 175

Gly Asp Ser Glu Ser Val Pro Asp Pro Gln Pro Leu Gly Glu Pro Pro

180 185 190

Ala Ala Pro Ser Gly Leu Gly Pro Asn Thr Met Ala Ser Gly Gly Gly

195 200 205

Ala Pro Met Ala Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Asn Ser

210 215 220

Ser Gly Asn Trp His Cys Asp Ser Thr Trp Leu Gly Asp Arg Val Ile

225 230 235 240

Thr Thr Ser Thr Arg Thr Trp Ala Leu Pro Thr Tyr Asn Asn His Leu

245 250 255

Tyr Lys Gln Ile Ser Asn Gly Thr Ser Gly Gly Ser Thr Asn Asp Asn

260 265 270

Thr Tyr Phe Gly Tyr Ser Thr Pro Trp Gly Tyr Phe Asp Phe Asn Arg

275 280 285

Phe His Cys His Phe Ser Pro Arg Asp Trp Gln Arg Leu Ile Asn Asn

290 295 300

Asn Trp Gly Phe Arg Pro Lys Arg Leu Asn Phe Lys Leu Phe Asn Ile

305 310 315 320

Gln Val Lys Glu Val Thr Thr Asn Glu Gly Thr Lys Thr Ile Ala Asn

325 330 335

Asn Leu Thr Ser Thr Val Gln Val Phe Thr Asp Ser Glu Tyr Gln Leu

340 345 350

Pro Tyr Val Leu Gly Ser Ala His Gln Gly Cys Leu Pro Pro Phe Pro

355 360 365

Ala Asp Val Phe Met Val Pro Gln Tyr Gly Tyr Leu Thr Leu Asn Asn

370 375 380

Gly Ser Gln Ala Leu Gly Arg Ser Ser Phe Tyr Cys Leu Glu Tyr Phe

385 390 395 400

Pro Ser Gln Met Leu Arg Thr Gly Asn Asn Phe Gln Phe Ser Tyr Thr

405 410 415

Phe Glu Asp Val Pro Phe His Ser Ser Tyr Ala His Ser Gln Ser Leu

420 425 430

Asp Arg Leu Met Asn Pro Leu Ile Asp Gln Tyr Leu Tyr Tyr Leu Val

435 440 445

Arg Thr Gln Thr Thr Gly Thr Gly Gly Thr Gln Thr Leu Ala Phe Ser

450 455 460

Gln Ala Gly Pro Ser Ser Met Ala Asn Gln Ala Arg Asn Trp Val Pro

465 470 475 480

Gly Pro Cys Tyr Arg Gln Gln Arg Val Ser Thr Thr Thr Asn Gln Asn

485 490 495

Asn Asn Ser Asn Phe Ala Trp Thr Gly Ala Ala Lys Phe Lys Leu Asn

500 505 510

Gly Arg Asp Ser Leu Met Asn Pro Gly Val Ala Met Ala Ser His Lys

515 520 525

Asp Asp Asp Asp Arg Phe Phe Pro Ser Ser Gly Val Leu Ile Phe Gly

530 535 540

Lys Gln Gly Ala Gly Asn Asp Gly Val Asp Tyr Ser Gln Val Leu Ile

545 550 555 560

Thr Asp Glu Glu Glu Ile Lys Ala Thr Asn Pro Val Ala Thr Glu Glu

565 570 575

Tyr Gly Ala Val Ala Ile Asn Asn Gln Ala Ala Asn Thr Gln Ala Gln

580 585 590

Thr Gly Leu Val His Asn Gln Gly Val Ile Pro Gly Met Val Trp Gln

595 600 605

Asn Arg Asp Val Tyr Leu Gln Gly Pro Ile Trp Ala Lys Ile Pro His

610 615 620

Thr Asp Gly Asn Phe His Pro Ser Pro Leu Met Gly Gly Phe Gly Leu

625 630 635 640

Lys His Pro Pro Pro Gln Ile Leu Ile Lys Asn Thr Pro Val Pro Ala

645 650 655

Asp Pro Pro Leu Thr Phe Asn Gln Ala Lys Leu Asn Ser Phe Ile Thr

660 665 670

Gln Tyr Ser Thr Gly Gln Val Ser Val Glu Ile Glu Trp Glu Leu Gln

675 680 685

Lys Glu Asn Ser Lys Arg Trp Asn Pro Glu Ile Gln Tyr Thr Ser Asn

690 695 700

Tyr Tyr Lys Ser Thr Asn Val Asp Phe Ala Val Asn Thr Glu Gly Val

705 710 715 720

Tyr Ser Glu Pro Arg Pro Ile Gly Thr Arg Tyr Leu Thr Arg Asn Leu

725 730 735

<210> 42

<211> 735

<212> PRT

<213> capsid protein of adeno-associated virus, hu.29

<400> 42

Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Thr Leu Ser

1 5 10 15

Glu Gly Ile Arg Gln Trp Trp Lys Leu Lys Pro Gly Pro Pro Pro Pro

20 25 30

Lys Pro Ala Glu Arg His Lys Asp Asp Ser Arg Gly Leu Val Leu Pro

35 40 45

Gly Tyr Lys Tyr Leu Gly Pro Phe Asn Gly Leu Asp Lys Gly Glu Pro

50 55 60

Val Asn Glu Ala Asp Ala Ala Ala Leu Glu His Asp Lys Ala Tyr Asp

65 70 75 80

Arg Gln Leu Asp Ser Gly Asp Asn Pro Tyr Leu Lys Tyr Asn His Ala

85 90 95

Asp Ala Glu Phe Gln Glu Arg Leu Lys Glu Asp Thr Ser Phe Gly Gly

100 105 110

Asn Leu Gly Arg Ala Val Phe Gln Ala Lys Lys Arg Val Leu Glu Pro

115 120 125

Leu Gly Leu Val Glu Glu Pro Val Lys Thr Ala Pro Gly Lys Lys Arg

130 135 140

Pro Val Glu His Ser Pro Ala Glu Pro Asp Ser Ser Ser Gly Thr Gly

145 150 155 160

Lys Ser Gly Asn Gln Pro Ala Arg Lys Arg Leu Asn Phe Gly Gln Thr

165 170 175

Gly Asp Ser Asp Ser Val Pro Asp Pro Gln Pro Leu Gly Gln Pro Pro

180 185 190

Ala Ala Pro Ser Gly Leu Gly Thr Asn Thr Met Ala Thr Gly Ser Gly

195 200 205

Ala Pro Met Ala Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Asn Ser

210 215 220

Ser Gly Asn Trp His Cys Asp Ser Thr Trp Met Gly Asp Arg Val Ile

225 230 235 240

Thr Thr Ser Thr Arg Thr Trp Ala Leu Pro Thr Tyr Asn Asn His Leu

245 250 255

Tyr Lys Gln Ile Ser Ser Gln Ser Gly Ala Ser Asn Asp Asn His Tyr

260 265 270

Phe Gly Tyr Ser Thr Pro Trp Gly Tyr Phe Asp Phe Asn Arg Phe His

275 280 285

Cys His Phe Ser Pro Arg Asp Trp Gln Arg Leu Ile Asn Asn Asn Trp

290 295 300

Gly Phe Arg Pro Lys Arg Leu Asn Phe Lys Leu Phe Asn Ile Gln Val

305 310 315 320

Lys Glu Val Thr Gln Asn Asp Gly Thr Thr Thr Ile Ala Asn Asn Leu

325 330 335

Thr Ser Thr Val Gln Val Phe Thr Asp Ser Glu Tyr Gln Leu Pro Tyr

340 345 350

Val Leu Gly Ser Ala His Gln Gly Cys Leu Pro Pro Phe Pro Ala Asp

355 360 365

Val Phe Met Val Pro Gln Tyr Gly Tyr Leu Thr Leu Asn Asn Gly Ser

370 375 380

Gln Ala Val Gly Arg Ser Ser Phe Tyr Cys Leu Gly Tyr Phe Pro Ser

385 390 395 400

Gln Met Leu Arg Thr Gly Asn Asn Phe Thr Phe Ser Tyr Thr Phe Glu

405 410 415

Asp Val Pro Phe His Ser Ser Tyr Ala His Ser Gln Ser Leu Asp Arg

420 425 430

Leu Met Asn Pro Leu Ile Asp Gln Tyr Leu Tyr Tyr Leu Ser Arg Thr

435 440 445

Asn Thr Pro Ser Gly Thr Thr Thr Gln Ser Arg Leu Gln Phe Ser Gln

450 455 460

Ala Gly Ala Ser Asp Ile Arg Asp Gln Ser Arg Asn Trp Leu Pro Gly

465 470 475 480

Pro Cys Tyr Arg Gln Gln Arg Val Ser Lys Thr Ser Ala Asp Asn Asn

485 490 495

Asn Ser Glu Tyr Ser Trp Thr Gly Ala Thr Lys Tyr His Leu Asn Gly

500 505 510

Arg Asp Ser Leu Val Asn Pro Gly Pro Ala Met Ala Ser His Lys Asp

515 520 525

Asp Glu Glu Lys Phe Phe Pro Gln Ser Gly Val Leu Ile Phe Gly Lys

530 535 540

Gln Gly Pro Glu Lys Thr Asn Val Asp Ile Glu Lys Val Met Ile Thr

545 550 555 560

Asp Glu Glu Glu Ile Arg Thr Thr Asn Pro Val Ala Thr Glu Gln Tyr

565 570 575

Gly Ser Val Ser Thr Asn Leu Gln Ser Gly Asn Thr Gln Ala Ala Thr

580 585 590

Ala Asp Val Asn Thr Gln Gly Val Leu Pro Gly Met Val Trp Gln Asp

595 600 605

Arg Asp Val Tyr Leu Gln Gly Pro Ile Trp Ala Lys Ile Pro His Thr

610 615 620

Asp Gly His Phe His Pro Ser Pro Leu Met Gly Gly Phe Gly Leu Lys

625 630 635 640

His Pro Pro Pro Gln Ile Leu Ile Lys Asn Thr Pro Val Pro Ala Asn

645 650 655

Pro Ser Thr Thr Phe Ser Ala Ala Lys Phe Ala Ser Phe Ile Thr Gln

660 665 670

Tyr Ser Thr Gly Gln Val Ser Val Glu Ile Glu Trp Glu Leu Gln Lys

675 680 685

Glu Asn Ser Lys Arg Trp Asn Pro Glu Ile Gln Tyr Thr Ser Asn Tyr

690 695 700

Asn Lys Ser Val Asn Val Asp Phe Thr Val Asp Thr Asn Gly Val Tyr

705 710 715 720

Ser Glu Pro Arg Pro Ile Gly Thr Arg Tyr Leu Thr Arg Asn Leu

725 730 735

<210> 43

<211> 738

<212> PRT

<213> capsid protein of macaque gland-associated virus, rh.64

<400> 43

Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser

1 5 10 15

Glu Gly Ile Arg Glu Trp Trp Asp Leu Lys Pro Gly Ala Pro Lys Pro

20 25 30

Lys Ala Asn Gln Gln Lys Gln Asp Asp Gly Arg Gly Leu Val Leu Pro

35 40 45

Gly Tyr Lys Tyr Leu Gly Pro Phe Asn Gly Leu Asp Lys Gly Glu Pro

50 55 60

Val Asn Ala Ala Asp Ala Ala Ala Leu Glu His Asp Lys Ala Tyr Asp

65 70 75 80

Gln Gln Leu Lys Ala Gly Asp Asn Pro Tyr Leu Arg Tyr Asn His Ala

85 90 95

Asp Ala Glu Phe Gln Glu Arg Leu Gln Glu Asp Thr Ser Phe Gly Gly

100 105 110

Asn Leu Gly Arg Ala Val Phe Gln Ala Lys Lys Arg Val Leu Glu Pro

115 120 125

Leu Gly Leu Val Glu Glu Gly Ala Lys Thr Ala Pro Gly Lys Lys Arg

130 135 140

Pro Val Glu Pro Ser Pro Gln Arg Ser Pro Asp Ser Ser Thr Gly Ile

145 150 155 160

Gly Lys Lys Gly Gln Gln Pro Ala Arg Lys Arg Leu Asn Phe Gly Gln

165 170 175

Thr Gly Asp Ser Glu Ser Val Pro Asp Pro Gln Pro Ile Gly Glu Pro

180 185 190

Pro Ala Ala Pro Ser Ser Val Gly Ser Gly Thr Met Ala Ala Gly Gly

195 200 205

Gly Ala Pro Met Ala Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Ser

210 215 220

Ser Ser Gly Asn Trp His Cys Asp Ser Thr Trp Leu Gly Asp Arg Val

225 230 235 240

Ile Thr Thr Ser Thr Arg Thr Trp Ala Leu Pro Thr Tyr Asn Asn His

245 250 255

Leu Tyr Lys Gln Ile Ser Asn Gly Thr Ser Gly Gly Ser Thr Asn Asp

260 265 270

Asn Thr Tyr Phe Gly Tyr Ser Thr Pro Trp Gly Tyr Phe Asp Phe Asn

275 280 285

Arg Phe His Cys His Phe Ser Pro Arg Asp Trp Gln Arg Leu Ile Asn

290 295 300

Asn Asn Trp Gly Phe Arg Pro Lys Arg Leu Ser Phe Lys Leu Phe Asn

305 310 315 320

Ile Gln Val Lys Glu Val Thr Gln Asn Glu Gly Thr Lys Thr Ile Ala

325 330 335

Asn Asn Leu Thr Ser Thr Ile Gln Val Phe Thr Asp Ser Glu Tyr Gln

340 345 350

Leu Pro Tyr Val Leu Gly Ser Ala His Gln Gly Cys Leu Pro Pro Phe

355 360 365

Pro Ala Asp Val Phe Met Ile Pro Gln Tyr Gly Tyr Leu Thr Leu Asn

370 375 380

Asn Gly Ser Gln Ala Val Gly Arg Ser Ser Phe Tyr Cys Leu Glu Tyr

385 390 395 400

Phe Pro Ser Gln Met Leu Arg Thr Gly Asn Asn Phe Ser Phe Ser Tyr

405 410 415

Thr Phe Glu Asp Val Pro Phe His Ser Ser Tyr Ala His Ser Gln Ser

420 425 430

Leu Asp Arg Leu Met Asn Pro Leu Ile Asp Gln Tyr Leu Tyr Tyr Leu

435 440 445

Ser Arg Thr Gln Ser Thr Gly Gly Thr Ala Gly Thr Gln Gln Leu Leu

450 455 460

Phe Ser Gln Ala Gly Pro Ser Asn Met Ser Ala Gln Ala Arg Asn Trp

465 470 475 480

Leu Pro Gly Pro Cys Tyr Arg Gln Gln Arg Val Ser Thr Thr Leu Ser

485 490 495

Gln Asn Asn Asn Ser Asn Phe Ala Trp Thr Gly Ala Thr Lys Tyr His

500 505 510

Leu Asn Gly Arg Asp Ser Leu Val Asn Pro Gly Val Ala Met Ala Thr

515 520 525

Asn Lys Asp Asp Glu Asp Arg Phe Phe Pro Ser Ser Gly Ile Leu Met

530 535 540

Phe Gly Lys Gln Gly Ala Gly Lys Asp Asn Val Asp Tyr Ser Asn Val

545 550 555 560

Met Leu Thr Ser Glu Glu Glu Ile Lys Thr Thr Asn Pro Val Ala Thr

565 570 575

Glu Gln Tyr Gly Val Val Ala Asp Asn Leu Gln Gln Gln Asn Thr Ala

580 585 590

Pro Ile Val Gly Ala Val Asn Ser Gln Gly Ala Leu Pro Gly Met Val

595 600 605

Trp Gln Asn Arg Asp Val Tyr Leu Gln Gly Pro Ile Trp Ala Lys Ile

610 615 620

Pro His Thr Asp Gly Asn Phe His Pro Ser Pro Leu Met Gly Gly Phe

625 630 635 640

Gly Leu Lys His Pro Pro Pro Gln Ile Leu Ile Lys Asn Thr Pro Val

645 650 655

Pro Ala Asp Pro Pro Thr Ala Phe Asn Gln Ala Lys Leu Asn Ser Phe

660 665 670

Ile Thr Gln Tyr Ser Thr Gly Gln Val Ser Val Glu Ile Val Trp Glu

675 680 685

Leu Gln Lys Glu Asn Ser Lys Arg Arg Asn Pro Glu Ile Gln Tyr Thr

690 695 700

Ser Asn Tyr Tyr Lys Ser Thr Asn Val Asp Phe Ala Val Asn Thr Glu

705 710 715 720

Gly Val Tyr Ser Glu Pro Arg Pro Ile Gly Thr Arg Tyr Leu Thr Arg

725 730 735

Asn Leu

<210> 44

<211> 737

<212> PRT

<213> capsid protein of macaque gland-associated virus, rh.48

<400> 44

Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser

1 5 10 15

Glu Gly Ile Arg Glu Trp Trp Asp Leu Lys Pro Gly Ala Pro Lys Pro

20 25 30

Lys Ala Asn Gln Gln Lys Gln Asp Asp Gly Arg Gly Leu Val Leu Pro

35 40 45

Gly Tyr Lys Tyr Leu Gly Pro Phe Asn Gly Leu Asp Lys Gly Glu Pro

50 55 60

Val Asn Ala Ala Asp Ala Ala Ala Leu Glu His Asp Lys Ala Tyr Asp

65 70 75 80

Gln Gln Leu Lys Ala Gly Asp Asn Pro Tyr Leu Arg Tyr Asn His Ala

85 90 95

Asp Ala Glu Phe Gln Glu Arg Leu Gln Glu Asp Thr Ser Phe Gly Gly

100 105 110

Asn Leu Gly Arg Ala Val Phe Gln Ala Lys Lys Arg Val Leu Glu Pro

115 120 125

Leu Gly Leu Val Glu Glu Ala Ala Lys Thr Ala Pro Gly Lys Lys Arg

130 135 140

Pro Val Glu Pro Ser Pro Gln Arg Ser Pro Asp Ser Ser Thr Gly Ile

145 150 155 160

Gly Lys Lys Gly Gln Gln Pro Ala Arg Lys Arg Leu Asn Phe Gly Gln

165 170 175

Thr Gly Asp Ser Glu Ser Val Pro Asp Pro Gln Pro Ile Gly Glu Pro

180 185 190

Pro Ala Gly Pro Ser Gly Leu Gly Ser Gly Thr Met Ala Ala Gly Gly

195 200 205

Gly Ala Pro Met Ala Asp Asn Asn Lys Gly Ala Asp Gly Val Gly Asn

210 215 220

Ala Ser Gly Asn Trp His Cys Asp Ser Thr Trp Leu Gly Asp Arg Val

225 230 235 240

Ile Thr Thr Ser Thr Arg Thr Trp Ala Leu Pro Thr Tyr Asn Asn His

245 250 255

Leu Tyr Lys Gln Ile Ser Ser Gln Ser Ala Gly Ser Thr Asn Asp Asn

260 265 270

Val Tyr Phe Gly Tyr Ser Thr Pro Trp Gly Tyr Phe Asp Phe Asn Arg

275 280 285

Phe His Cys His Phe Ser Pro Arg Asp Trp Gln Arg Leu Ile Asn Ser

290 295 300

Asn Trp Gly Phe Arg Pro Lys Lys Leu Asn Phe Lys Leu Phe Asn Ile

305 310 315 320

Gln Val Lys Glu Val Thr Thr Asn Asp Gly Val Thr Thr Ile Ala Asn

325 330 335

Asn Leu Thr Ser Thr Val Gln Val Phe Ser Asp Ser Glu Tyr Gln Leu

340 345 350

Pro Tyr Val Leu Gly Ser Ala His Gln Gly Cys Leu Pro Pro Phe Pro

355 360 365

Ala Asp Val Phe Met Ile Pro Gln Tyr Gly Tyr Leu Thr Leu Asn Asn

370 375 380

Gly Ser Gln Ser Val Gly Arg Ser Ser Phe Tyr Cys Leu Glu Tyr Phe

385 390 395 400

Pro Ser Gln Met Leu Arg Thr Gly Asn Asn Phe Thr Phe Ser Tyr Thr

405 410 415

Phe Glu Asp Val Pro Phe His Ser Ser Tyr Ala His Ser Gln Ser Leu

420 425 430

Asp Arg Leu Met Asn Pro Leu Ile Asp Gln Tyr Leu Tyr Tyr Leu Ala

435 440 445

Arg Thr Gln Ser Asn Ala Gly Gly Thr Ala Gly Asn Arg Glu Leu Gln

450 455 460

Phe Tyr Gln Gly Gly Pro Thr Thr Met Ala Glu Gln Ala Lys Asn Trp

465 470 475 480

Leu Pro Gly Pro Cys Phe Arg Gln Gln Arg Val Ser Lys Thr Leu Asp

485 490 495

Gln Asn Asn Asn Ser Asn Phe Ala Trp Thr Gly Ala Thr Lys Tyr His

500 505 510

Leu Asn Gly Arg Asn Ser Leu Val Asn Pro Gly Val Ala Met Ala Thr

515 520 525

His Lys Asp Asp Glu Glu Arg Phe Phe Pro Ser Ser Gly Val Leu Ile

530 535 540

Phe Gly Lys Thr Gly Ala Ala Asn Lys Thr Thr Leu Glu Asn Val Leu

545 550 555 560

Met Thr Asn Glu Glu Glu Ile Arg Pro Thr Asn Pro Val Ala Thr Glu

565 570 575

Glu Tyr Gly Thr Val Ser Ser Asn Leu Gln Ala Ala Asn Thr Ala Ala

580 585 590

Gln Thr Gln Val Val Asn Asn Gln Gly Ala Leu Pro Gly Met Val Trp

595 600 605

Gln Asn Arg Asp Val Tyr Leu Gln Gly Pro Ile Trp Ala Lys Ile Pro

610 615 620

His Thr Asp Gly Asn Phe His Pro Ser Pro Leu Met Gly Gly Phe Gly

625 630 635 640

Leu Lys His Pro Pro Pro Gln Ile Leu Ile Lys Asn Thr Pro Val Pro

645 650 655

Ala Asn Pro Pro Glu Val Phe Thr Pro Ala Lys Phe Ala Ser Phe Ile

660 665 670

Thr Gln Tyr Ser Thr Gly Gln Val Ser Val Glu Ile Glu Trp Glu Leu

675 680 685

Gln Lys Glu Asn Ser Lys Arg Trp Asn Pro Glu Ile Gln Tyr Thr Ser

690 695 700

Asn Phe Asp Lys Gln Thr Gly Val Asp Phe Ala Val Asp Ser Gln Gly

705 710 715 720

Val Tyr Ser Glu Pro Arg Pro Ile Gly Thr Arg Tyr Leu Thr Arg Asn

725 730 735

Leu

<210> 45

<211> 736

<212> PRT

<213> capsid protein of adeno-associated virus, hu.44

<400> 45

Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Thr Leu Ser

1 5 10 15

Glu Gly Ile Arg Gln Trp Trp Lys Leu Arg Pro Gly Pro Pro Pro Pro

20 25 30

Lys Pro Ala Glu Arg His Lys Asp Asp Ser Arg Gly Leu Val Leu Pro

35 40 45

Gly Tyr Lys Tyr Leu Gly Pro Phe Asn Gly Leu Asp Lys Gly Glu Pro

50 55 60

Val Asn Glu Ala Asp Ala Ala Ala Leu Glu His Asp Lys Ala Tyr Asp

65 70 75 80

Arg Gln Leu Asp Ser Gly Asp Asn Pro Tyr Leu Lys Tyr Asn His Ala

85 90 95

Asp Ala Glu Phe Gln Glu Arg Leu Lys Glu Asp Thr Ser Phe Gly Gly

100 105 110

Asn Leu Gly Arg Ala Val Phe Gln Ala Lys Lys Arg Val Leu Glu Pro

115 120 125

Leu Gly Leu Val Glu Glu Gly Ala Glu Thr Ala Pro Gly Lys Lys Arg

130 135 140

Pro Val Glu Gln Ser Pro Gln Gly Pro Asp Ser Ser Ser Gly Ile Gly

145 150 155 160

Lys Thr Gly Gln Gln Pro Ala Lys Lys Arg Leu Asn Phe Gly Gln Thr

165 170 175

Gly Asp Ser Glu Ser Val Pro Asp Pro Gln Pro Leu Gly Glu Pro Pro

180 185 190

Ala Thr Pro Ala Ala Val Gly Pro Thr Thr Met Ala Ser Gly Gly Gly

195 200 205

Ala Pro Met Ala Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Asn Ala

210 215 220

Ser Gly Asn Trp His Cys Asp Ser Thr Trp Leu Gly Asp Arg Val Ile

225 230 235 240

Thr Thr Ser Thr Arg Thr Trp Ala Leu Pro Thr Tyr Asn Asn His Leu

245 250 255

Tyr Lys Gln Ile Ser Ser Ala Ser Thr Gly Ala Ser Asn Asp Asn His

260 265 270

Tyr Phe Gly Tyr Ser Thr Pro Trp Gly Tyr Phe Asp Phe Asn Arg Phe

275 280 285

His Cys His Phe Ser Pro Arg Asp Trp Gln Arg Leu Ile Asn Asn Asn

290 295 300

Trp Gly Phe Arg Pro Lys Arg Leu Asn Phe Lys Leu Phe Asn Ile Gln

305 310 315 320

Val Lys Glu Val Thr Thr Asn Asp Gly Val Thr Thr Ile Ala Asn Asn

325 330 335

Leu Thr Ser Thr Val Gln Val Phe Ser Asp Ser Glu Tyr Gln Leu Pro

340 345 350

Tyr Val Leu Gly Ser Ala His Gln Gly Cys Leu Pro Pro Phe Pro Ala

355 360 365

Asp Val Phe Met Ile Pro Gln Tyr Gly Tyr Leu Thr Leu Asn Asn Gly

370 375 380

Ser Gln Ala Val Gly Arg Ser Ser Phe Tyr Cys Leu Glu Tyr Phe Pro

385 390 395 400

Ser Gln Met Leu Arg Thr Gly Asn Asn Phe Thr Phe Ser Tyr Thr Phe

405 410 415

Glu Glu Val Pro Phe His Ser Ser Tyr Ala His Ser Gln Ser Leu Asp

420 425 430

Arg Leu Met Asn Pro Leu Ile Asp Gln Tyr Leu Tyr Tyr Pro Asn Arg

435 440 445

Thr Gln Asn Gln Ser Gly Ser Ala Gln Asn Lys Asp Leu Leu Phe Ser

450 455 460

Arg Gly Ser Pro Ala Gly Met Ser Val Gln Pro Lys Asn Trp Leu Pro

465 470 475 480

Gly Pro Cys Tyr Arg Gln Gln Arg Val Ser Lys Thr Lys Thr Asp Asn

485 490 495

Asn Asn Ser Asn Phe Thr Trp Thr Gly Ala Ser Lys Tyr Asn Leu Asn

500 505 510

Gly Arg Glu Ser Ile Ile Asn Pro Gly Thr Ala Met Ala Ser His Lys

515 520 525

Asp Asp Glu Asp Lys Phe Phe Pro Met Ser Gly Val Met Ile Phe Gly

530 535 540

Lys Glu Ser Ala Gly Ala Ser Asn Thr Ala Leu Asp Asn Val Met Ile

545 550 555 560

Thr Asp Glu Glu Glu Ile Lys Ala Thr Asn Pro Val Ala Thr Glu Arg

565 570 575

Phe Gly Thr Val Ala Val Asn Phe Gln Ser Ser Ser Thr Asp Pro Ala

580 585 590

Thr Gly Asp Val His Ala Met Gly Ala Leu Pro Gly Met Val Trp Gln

595 600 605

Gly Arg Asp Val Tyr Leu Gln Gly Pro Ile Trp Ala Lys Ile Pro His

610 615 620

Thr Asp Gly His Phe His Pro Ser Pro Leu Met Gly Gly Phe Gly Leu

625 630 635 640

Lys Asn Pro Pro Pro Gln Ile Leu Ile Lys Asn Thr Pro Val Pro Ala

645 650 655

Asn Pro Pro Ala Glu Phe Ser Ala Thr Lys Phe Ala Ser Phe Ile Thr

660 665 670

Gln Tyr Ser Thr Gly Gln Val Ser Val Glu Ile Glu Trp Glu Leu Gln

675 680 685

Lys Glu Asn Ser Lys Arg Trp Asn Pro Glu Val Gln Tyr Thr Ser Asn

690 695 700

Tyr Ala Lys Ser Ala Asn Val Asp Phe Thr Val Asp Asn Asn Gly Leu

705 710 715 720

Tyr Thr Glu Pro Arg Pro Ile Gly Thr Arg Tyr Leu Thr Arg Pro Leu

725 730 735

<210> 46

<211> 735

<212> PRT

<213> capsid protein of ch.5

<400> 46

Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Thr Leu Ser

1 5 10 15

Glu Gly Ile Arg Gln Trp Trp Lys Leu Lys Pro Gly Pro Pro Pro Pro

20 25 30

Lys Pro Asn Gln Gln His Arg Asp Asp Ser Arg Gly Leu Val Leu Pro

35 40 45

Gly Tyr Lys Tyr Leu Gly Pro Phe Asn Gly Leu Asp Lys Gly Glu Pro

50 55 60

Val Asn Glu Ala Asp Ala Ala Ala Leu Glu His Asp Lys Ala Tyr Asp

65 70 75 80

His Gln Leu Lys Gln Gly Asp Asn Pro Tyr Leu Lys Tyr Asn His Ala

85 90 95

Asp Ala Glu Phe Gln Glu Arg Leu Gln Glu Asp Thr Ser Phe Gly Gly

100 105 110

Asn Leu Gly Arg Ala Val Phe Gln Ala Lys Lys Arg Val Leu Glu Pro

115 120 125

Leu Gly Leu Val Glu Glu Ala Val Lys Thr Ala Pro Gly Lys Lys Arg

130 135 140

Pro Ile Glu Gln Ser Pro Ala Glu Pro Asp Ser Ser Ser Gly Ile Gly

145 150 155 160

Lys Ser Gly Gln Gln Pro Ala Lys Lys Arg Leu Asn Phe Gly Gln Thr

165 170 175

Gly Asp Thr Glu Ser Val Pro Asp Pro Gln Pro Ile Gly Glu Pro Pro

180 185 190

Ala Ala Pro Ser Gly Val Gly Ser Asn Thr Met Ala Ser Gly Gly Gly

195 200 205

Ala Pro Met Ala Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Asn Ser

210 215 220

Ser Gly Asn Trp His Cys Asp Ser Thr Trp Met Gly Asp Arg Val Ile

225 230 235 240

Thr Thr Ser Thr Arg Thr Trp Ala Leu Pro Thr Tyr Asn Asn His Leu

245 250 255

Tyr Lys Gln Ile Ser Ser Glu Ser Gly Ala Thr Asn Asp Asn His Tyr

260 265 270

Phe Gly Tyr Ser Thr Pro Trp Gly Tyr Phe Asp Phe Asn Arg Phe His

275 280 285

Cys His Phe Ser Pro Arg Asp Trp Gln Arg Leu Ile Asn Asn Asn Trp

290 295 300

Gly Phe Arg Pro Lys Lys Leu Asn Phe Lys Leu Phe Asn Ile Gln Val

305 310 315 320

Lys Glu Val Thr Gln Asn Asp Gly Thr Thr Thr Ile Ala Asn Asn Leu

325 330 335

Thr Ser Thr Val Gln Val Phe Thr Asp Ser Glu Tyr Gln Leu Pro Tyr

340 345 350

Val Leu Gly Ser Ala His Gln Gly Cys Leu Pro Pro Phe Pro Ala Asp

355 360 365

Val Phe Met Ile Pro Gln Tyr Gly Tyr Leu Thr Leu Asn Asn Gly Ser

370 375 380

Gln Ala Val Gly Arg Ser Ser Phe Tyr Cys Leu Glu Tyr Phe Pro Ser

385 390 395 400

Gln Met Leu Arg Thr Gly Asn Asn Phe Thr Phe Ser Tyr Thr Phe Glu

405 410 415

Asp Val Pro Phe His Ser Ser Tyr Ala His Ser Gln Ser Leu Asp Arg

420 425 430

Leu Met Asn Pro Leu Ile Asp Gln Tyr Leu Tyr Tyr Leu Ser Lys Thr

435 440 445

Gln Gly Thr Ser Gly Thr Thr Gln Gln Ser Arg Leu Gln Phe Ser Gln

450 455 460

Ala Gly Pro Ser Ser Met Ala Gln Gln Ala Lys Asn Trp Leu Pro Gly

465 470 475 480

Pro Ser Tyr Arg Gln Gln Arg Met Ser Lys Thr Ala Asn Asp Asn Asn

485 490 495

Asn Ser Glu Phe Ala Trp Thr Ala Ala Thr Lys Tyr Tyr Leu Asn Gly

500 505 510

Arg Asn Ser Leu Val Asn Pro Gly Pro Pro Met Ala Ser His Lys Asp

515 520 525

Asp Glu Glu Lys Tyr Phe Pro Met His Gly Asn Leu Ile Phe Gly Lys

530 535 540

Gln Gly Thr Gly Thr Thr Asn Val Asp Ile Glu Ser Val Leu Ile Thr

545 550 555 560

Asp Glu Glu Glu Ile Arg Thr Thr Asn Pro Val Ala Thr Glu Gln Tyr

565 570 575

Gly Gln Val Ala Thr Asn His Gln Ser Gln Asn Thr Thr Ala Ser Tyr

580 585 590

Gly Ser Val Asp Ser Gln Gly Ile Leu Pro Gly Met Val Trp Gln Asp

595 600 605

Arg Asp Val Tyr Leu Gln Gly Pro Ile Trp Ala Lys Ile Pro His Thr

610 615 620

Asp Gly His Phe His Pro Ser Pro Leu Met Gly Gly Phe Gly Leu Lys

625 630 635 640

His Pro Pro Pro Gln Ile Leu Ile Lys Asn Thr Pro Val Pro Ala Asn

645 650 655

Pro Ala Thr Thr Phe Thr Pro Gly Lys Phe Ala Ser Phe Ile Thr Gln

660 665 670

Tyr Ser Thr Gly Gln Val Ser Val Glu Ile Glu Trp Glu Leu Gln Lys

675 680 685

Glu Asn Ser Lys Arg Trp Asn Pro Glu Ile Gln Tyr Thr Ser Asn Tyr

690 695 700

Asn Lys Ser Val Asn Val Glu Phe Thr Val Asp Ala Asn Gly Val Tyr

705 710 715 720

Ser Glu Pro Arg Pro Ile Gly Thr Arg Tyr Leu Thr Arg Asn Leu

725 730 735

<210> 47

<211> 737

<212> PRT

<213> capsid protein of macaque gland-associated virus, rh.67

<400> 47

Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser

1 5 10 15

Glu Gly Ile Arg Glu Trp Trp Asp Leu Lys Pro Gly Ala Pro Lys Pro

20 25 30

Lys Ala Asn Gln Gln Lys Gln Asp Asp Gly Arg Gly Leu Val Leu Pro

35 40 45

Gly Tyr Lys Tyr Leu Gly Pro Phe Asn Gly Leu Asp Lys Gly Glu Pro

50 55 60

Val Asn Ala Ala Asp Ala Ala Ala Leu Glu His Asp Lys Ala Tyr Asp

65 70 75 80

Gln Gln Leu Lys Ala Gly Asp Asn Pro Tyr Leu Arg Tyr Asn His Ala

85 90 95

Asp Ala Glu Phe Gln Glu Arg Leu Gln Glu Asp Thr Ser Phe Gly Gly

100 105 110

Asn Leu Gly Arg Ala Val Leu Gln Ala Lys Lys Arg Val Leu Glu Pro

115 120 125

Leu Gly Leu Val Glu Glu Ala Ala Lys Thr Ala Pro Gly Lys Lys Arg

130 135 140

Pro Val Glu Pro Ser Pro Gln Arg Ser Pro Asp Ser Ser Thr Gly Ile

145 150 155 160

Gly Lys Lys Gly Gln Gln Pro Ala Arg Lys Arg Leu Asn Phe Gly Gln

165 170 175

Thr Gly Asp Ser Glu Ser Val Pro Asp Pro Gln Pro Ile Gly Glu Pro

180 185 190

Pro Ala Gly Pro Ser Gly Leu Gly Ser Gly Thr Met Ala Ala Gly Gly

195 200 205

Gly Ala Pro Met Ala Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Asn

210 215 220

Ala Ser Gly Asn Trp His Cys Asp Ser Thr Trp Leu Gly Asp Arg Val

225 230 235 240

Ile Thr Thr Ser Thr Arg Thr Trp Ala Leu Pro Thr Tyr Asn Asn His

245 250 255

Leu Tyr Lys Gln Ile Ser Ser Gln Ser Ala Gly Ser Thr Asn Asp Asn

260 265 270

Val Tyr Phe Gly Tyr Ser Thr Pro Trp Gly Tyr Phe Asp Phe Asn Arg

275 280 285

Phe His Cys His Phe Ser Pro Arg Asp Trp Gln Arg Leu Ile Asn Asn

290 295 300

Asn Trp Gly Phe Arg Pro Lys Lys Leu Asn Phe Lys Leu Phe Asn Ile

305 310 315 320

Gln Val Lys Glu Val Thr Thr Asn Asp Gly Val Thr Thr Ile Ala Asn

325 330 335

Asn Leu Thr Ser Thr Val Gln Val Phe Ser Asp Ser Glu Tyr Gln Leu

340 345 350

Pro Tyr Val Leu Gly Ser Ala His Gln Gly Cys Leu Pro Pro Phe Pro

355 360 365

Ala Asp Val Phe Met Ile Pro Gln Tyr Gly Tyr Leu Thr Leu Asn Asn

370 375 380

Gly Ser Gln Ser Val Gly Arg Ser Ser Phe Tyr Cys Leu Glu Tyr Phe

385 390 395 400

Pro Ser Gln Met Leu Arg Thr Gly Asn Asn Phe Thr Phe Ser Tyr Thr

405 410 415

Phe Glu Asp Val Pro Phe His Ser Ser Tyr Ala His Ser Gln Ser Leu

420 425 430

Asp Arg Leu Met Asn Pro Leu Ile Asp Gln Tyr Leu Tyr Tyr Leu Ala

435 440 445

Arg Thr Gln Ser Asn Ala Gly Gly Thr Ala Gly Asn Arg Glu Leu Gln

450 455 460

Phe Tyr Gln Gly Gly Pro Thr Thr Met Ala Glu Gln Ala Lys Asn Trp

465 470 475 480

Leu Pro Gly Pro Cys Phe Arg Gln Gln Arg Val Ser Lys Thr Leu Asp

485 490 495

Gln Asn Asn Asn Ser Asn Phe Ala Trp Thr Gly Ala Thr Lys Tyr His

500 505 510

Leu Asn Gly Arg Asn Ser Leu Val Asn Pro Gly Val Ala Met Ala Thr

515 520 525

His Lys Asp Asp Glu Glu Arg Phe Phe Pro Ser Ser Gly Val Leu Ile

530 535 540

Phe Gly Lys Thr Gly Ala Ala Asn Lys Thr Thr Leu Glu Asn Val Leu

545 550 555 560

Met Thr Asn Glu Glu Glu Ile Arg Pro Thr Asn Pro Val Ala Thr Glu

565 570 575

Glu Tyr Gly Thr Val Ser Ser Asn Leu Gln Ala Ala Asn Thr Ala Ala

580 585 590

Gln Thr Gln Val Val Asn Asn Gln Gly Ala Leu Pro Gly Met Val Trp

595 600 605

Gln Asn Arg Asp Val Tyr Leu Gln Gly Pro Ile Trp Ala Lys Ile Pro

610 615 620

His Thr Asp Gly Asn Phe His Pro Ser Pro Leu Met Gly Gly Phe Gly

625 630 635 640

Leu Lys His Pro Pro Pro Gln Ile Leu Ile Lys Asn Thr Pro Val Pro

645 650 655

Ala Asn Pro Pro Glu Val Phe Thr Pro Ala Lys Phe Ala Ser Phe Ile

660 665 670

Thr Gln Tyr Ser Thr Gly Gln Val Ser Val Glu Ile Glu Trp Glu Leu

675 680 685

Gln Lys Glu Asn Ser Lys Arg Trp Asn Pro Glu Ile Gln Tyr Thr Ser

690 695 700

Asn Phe Asp Lys Gln Thr Gly Val Asp Phe Ala Val Asp Ser Gln Gly

705 710 715 720

Val Tyr Ser Glu Pro Arg Pro Ile Gly Thr Arg Tyr Leu Thr Arg Asn

725 730 735

Leu

<210> 48

<211> 738

<212> PRT

<213> capsid protein of macaque gland-associated virus, rh.58

<400> 48

Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser

1 5 10 15

Glu Gly Ile Arg Glu Trp Trp Asp Leu Lys Pro Gly Ala Pro Lys Pro

20 25 30

Lys Ala Asn Gln Gln Lys Gln Asp Asp Gly Arg Gly Leu Val Leu Pro

35 40 45

Gly Tyr Lys Tyr Leu Gly Pro Phe Asn Gly Leu Asp Lys Gly Glu Pro

50 55 60

Val Asn Ala Ala Asp Ala Ala Ala Leu Glu His Asp Lys Ala Tyr Asp

65 70 75 80

Gln Gln Leu Lys Ala Gly Asp Asn Pro Tyr Leu Arg Tyr Asn His Ala

85 90 95

Asp Ala Glu Phe Gln Glu Arg Leu Gln Glu Asp Thr Ser Phe Gly Gly

100 105 110

Asn Leu Gly Arg Ala Val Phe Gln Ala Lys Lys Arg Val Leu Glu Pro

115 120 125

Leu Gly Leu Val Glu Glu Ala Ala Lys Thr Ala Pro Gly Lys Lys Arg

130 135 140

Pro Val Glu Pro Ser Pro Gln Arg Ser Pro Asp Ser Ser Thr Gly Ile

145 150 155 160

Gly Lys Lys Gly Gln Gln Pro Ala Arg Lys Arg Leu Asn Phe Gly Gln

165 170 175

Thr Gly Asp Ser Glu Ser Val Pro Asp Pro Gln Pro Ile Gly Glu Pro

180 185 190

Pro Ala Ala Pro Ser Ser Val Gly Ser Gly Thr Met Ala Ala Gly Gly

195 200 205

Gly Ala Pro Met Ala Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Ser

210 215 220

Ser Ser Gly Asn Trp His Cys Asp Ser Thr Trp Leu Gly Asp Arg Val

225 230 235 240

Ile Thr Thr Ser Thr Arg Thr Trp Ala Leu Pro Thr Tyr Asn Asn His

245 250 255

Leu Tyr Lys Gln Ile Ser Asn Gly Thr Ser Gly Gly Ser Thr Asn Asp

260 265 270

Asn Thr Tyr Phe Gly Tyr Ser Thr Pro Trp Gly Tyr Phe Asp Phe Asn

275 280 285

Arg Phe His Cys His Phe Ser Pro Arg Asp Trp Gln Arg Leu Ile Asn

290 295 300

Asn Asn Trp Gly Phe Arg Pro Lys Arg Leu Ser Phe Lys Leu Phe Asn

305 310 315 320

Ile Gln Val Lys Glu Val Thr Gln Asn Glu Gly Thr Lys Thr Ile Ala

325 330 335

Asn Asn Leu Thr Ser Thr Ile Gln Val Phe Thr Asp Ser Glu Tyr Gln

340 345 350

Leu Pro Tyr Val Leu Gly Ser Ala His Gln Gly Cys Leu Pro Pro Phe

355 360 365

Pro Ala Asp Val Phe Met Ile Pro Gln Tyr Gly Tyr Leu Thr Leu Asn

370 375 380

Asn Gly Ser Gln Ala Val Gly Arg Ser Ser Phe Tyr Cys Leu Glu Tyr

385 390 395 400

Phe Pro Ser Gln Met Leu Arg Thr Gly Asn Asn Phe Ser Phe Ser Tyr

405 410 415

Thr Phe Glu Asp Val Pro Phe His Ser Ser Tyr Ala His Ser Gln Ser

420 425 430

Leu Asp Arg Leu Met Asn Pro Leu Ile Asp Gln Tyr Leu Tyr Tyr Leu

435 440 445

Ser Arg Thr Gln Ser Thr Gly Gly Thr Ala Gly Thr Gln Gln Leu Leu

450 455 460

Phe Ser Gln Ala Gly Pro Ser Asn Met Ser Ala Gln Ala Arg Asn Trp

465 470 475 480

Leu Pro Gly Pro Cys Tyr Arg Gln Gln Arg Val Ser Thr Thr Leu Ser

485 490 495

Gln Asn Asn Asn Ser Asn Phe Ala Trp Thr Gly Ala Thr Lys Tyr His

500 505 510

Leu Asn Gly Arg Asp Ser Leu Val Asn Pro Gly Val Ala Met Ala Thr

515 520 525

Asn Lys Asp Asp Glu Asp Arg Phe Phe Pro Ser Ser Gly Ile Leu Met

530 535 540

Phe Gly Lys Gln Gly Ala Gly Lys Asp Asn Val Asp Tyr Ser Asn Val

545 550 555 560

Met Leu Thr Ser Glu Glu Glu Ile Lys Thr Thr Asn Pro Val Ala Thr

565 570 575

Glu Gln Tyr Gly Val Val Ala Asp Asn Leu Gln Gln Gln Asn Thr Ala

580 585 590

Pro Ile Val Gly Ala Val Asn Ser Gln Gly Ala Leu Pro Gly Met Val

595 600 605

Trp Gln Asn Arg Asp Val Tyr Leu Gln Gly Pro Ile Trp Ala Lys Ile

610 615 620

Pro His Thr Asp Gly Asn Phe His Pro Ser Pro Leu Met Gly Gly Phe

625 630 635 640

Gly Leu Lys His Pro Pro Pro Gln Ile Leu Ile Lys Ser Thr Pro Val

645 650 655

Pro Ala Asp Pro Pro Thr Ala Phe Asn Gln Ala Lys Leu Asn Ser Phe

660 665 670

Ile Thr Gln Tyr Ser Thr Gly Gln Val Ser Val Glu Ile Glu Trp Glu

675 680 685

Leu Gln Lys Glu Asn Ser Lys Cys Trp Asn Pro Glu Ile Gln Tyr Thr

690 695 700

Ser Asn Tyr Tyr Lys Ser Thr Asn Val Asp Phe Ala Val Asn Thr Glu

705 710 715 720

Gly Val Tyr Ser Glu Pro Arg Pro Ile Gly Thr Arg Tyr Leu Thr Arg

725 730 735

Asn Leu

<210> 49

<211> 737

<212> PRT

<213> capsid protein of macaque gland-associated virus, rh.54

<400> 49

Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser

1 5 10 15

Glu Gly Ile Arg Glu Trp Trp Asp Leu Lys Pro Gly Ala Pro Lys Pro

20 25 30

Lys Ala Asn Gln Gln Lys Gln Asp Asp Gly Arg Gly Leu Val Leu Pro

35 40 45

Gly Tyr Lys Tyr Leu Gly Pro Phe Asn Gly Leu Asp Lys Gly Glu Pro

50 55 60

Val Asn Ala Ala Asp Ala Ala Ala Leu Glu His Asp Lys Ala Tyr Asp

65 70 75 80

Gln Gln Leu Lys Ala Gly Asp Asn Pro Tyr Leu Arg Tyr Asn His Ala

85 90 95

Asp Ala Glu Phe Gln Glu Arg Leu Gln Glu Asp Thr Ser Phe Gly Gly

100 105 110

Asn Leu Gly Arg Ala Val Phe Gln Ala Lys Lys Arg Val Leu Glu Pro

115 120 125

Leu Gly Leu Val Glu Glu Ala Ala Lys Thr Ala Pro Gly Lys Lys Arg

130 135 140

Pro Val Glu Pro Ser Pro Gln Arg Ser Pro Asp Ser Ser Thr Gly Ile

145 150 155 160

Gly Lys Lys Gly Gln Gln Pro Ala Arg Lys Arg Leu Asn Phe Gly Gln

165 170 175

Thr Gly Asp Ser Glu Ser Val Pro Asp Pro Gln Pro Leu Gly Glu Pro

180 185 190

Pro Ala Gly Pro Ser Gly Leu Gly Ser Gly Thr Met Ala Ala Gly Gly

195 200 205

Gly Ala Pro Met Ala Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Asn

210 215 220

Ala Ser Gly Asn Trp His Cys Asp Ser Thr Trp Leu Gly Asp Arg Val

225 230 235 240

Ile Thr Thr Ser Thr Arg Thr Trp Ala Leu Pro Thr Tyr Asn Asn His

245 250 255

Leu Tyr Lys Gln Ile Ser Ser Gln Ser Ala Gly Ser Thr Asn Asp Asn

260 265 270

Val Tyr Phe Gly Tyr Ser Thr Pro Trp Gly Tyr Phe Asp Phe Asn Arg

275 280 285

Phe His Cys His Phe Ser Pro Arg Asp Trp Gln Arg Leu Ile Asn Asn

290 295 300

Asn Trp Gly Phe Arg Pro Lys Lys Leu Asn Phe Lys Leu Phe Asn Ile

305 310 315 320

Gln Val Lys Glu Val Thr Thr Asn Asp Gly Val Thr Thr Ile Ala Asn

325 330 335

Asn Leu Thr Ser Thr Val Gln Val Phe Ser Asp Ser Glu Tyr Gln Leu

340 345 350

Pro Tyr Val Leu Gly Ser Ala His Gln Gly Cys Leu Pro Pro Phe Pro

355 360 365

Ala Asp Val Phe Met Ile Pro Gln Tyr Gly Tyr Leu Thr Leu Asn Asn

370 375 380

Gly Ser Gln Ser Val Gly Arg Ser Ser Phe Tyr Cys Leu Glu Tyr Phe

385 390 395 400

Pro Ser Gln Val Leu Arg Thr Gly Asn Asn Phe Thr Phe Ser Tyr Thr

405 410 415

Phe Glu Asp Val Pro Phe His Ser Ser Tyr Ala His Ser Gln Ser Leu

420 425 430

Asp Arg Leu Met Asn Pro Leu Ile Asp Gln Tyr Leu Tyr Tyr Leu Ala

435 440 445

Arg Thr Gln Ser Asn Pro Gly Gly Thr Ser Gly Asn Arg Glu Leu Gln

450 455 460

Phe Tyr Gln Gly Gly Pro Ser Thr Met Ala Glu Gln Ala Lys Asn Trp

465 470 475 480

Leu Pro Gly Pro Cys Phe Arg Gln Gln Arg Val Ser Lys Thr Leu Asp

485 490 495

Gln Asn Asn Asn Ser Asn Phe Ala Trp Thr Gly Ala Thr Lys Tyr His

500 505 510

Leu Asn Gly Arg Asn Ser Leu Val Asn Pro Gly Val Ala Met Ala Thr

515 520 525

His Lys Asp Asp Glu Asp Arg Phe Phe Pro Ser Ser Gly Val Leu Ile

530 535 540

Phe Gly Lys Thr Gly Ala Thr Asn Lys Thr Thr Leu Glu Asn Val Leu

545 550 555 560

Met Thr Asn Glu Glu Glu Ile Arg Pro Thr Asn Pro Val Ala Thr Glu

565 570 575

Glu Tyr Gly Ile Val Ser Ser Asn Leu Gln Ala Ala Asn Thr Ala Ala

580 585 590

Gln Thr Gln Val Val Asn Asn Gln Gly Ala Leu Pro Gly Met Val Trp

595 600 605

Gln Asn Arg Asp Val Tyr Leu Gln Gly Pro Ile Trp Ala Lys Ile Pro

610 615 620

His Thr Asp Gly Asn Phe His Pro Ser Pro Leu Met Gly Gly Phe Gly

625 630 635 640

Leu Lys His Pro Pro Pro Gln Ile Leu Ile Lys Asn Thr Pro Val Pro

645 650 655

Ala Asn Pro Pro Glu Val Phe Thr Pro Ala Lys Phe Ala Ser Phe Ile

660 665 670

Thr Gln Tyr Ser Thr Gly Gln Val Ser Val Glu Ile Glu Trp Glu Leu

675 680 685

Gln Lys Glu Asn Ser Lys Arg Trp Asn Pro Glu Ile Gln Tyr Thr Ser

690 695 700

Asn Phe Asp Lys Gln Thr Gly Val Asp Phe Ala Val Asp Ser Gln Gly

705 710 715 720

Val Tyr Ser Glu Pro Arg Pro Ile Gly Thr Arg Tyr Leu Thr Arg Asn

725 730 735

Leu

<210> 50

<211> 736

<212> PRT

<213> capsid protein of adeno-associated virus, hu.48

<400> 50

Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser

1 5 10 15

Glu Gly Ile Arg Glu Trp Trp Asp Leu Lys Pro Gly Ala Pro Lys Pro

20 25 30

Lys Ala Asn Gln Gln Lys Gln Asp Asp Gly Arg Gly Leu Val Leu Pro

35 40 45

Gly Tyr Lys Tyr Leu Gly Pro Phe Asn Gly Leu Asp Lys Gly Glu Pro

50 55 60

Val Asn Ala Ala Asp Ala Ala Ala Leu Glu His Asp Lys Ala Tyr Asp

65 70 75 80

Gln Gln Leu Lys Ala Gly Asp Asn Pro Tyr Leu Arg Tyr Asn His Ala

85 90 95

Asp Ala Glu Phe Gln Glu Arg Leu Gln Glu Asp Thr Ser Phe Gly Gly

100 105 110

Asn Leu Gly Arg Ala Val Phe Gln Ala Lys Lys Arg Val Leu Glu Pro

115 120 125

Leu Gly Leu Val Glu Glu Gly Ala Lys Thr Ala Pro Gly Lys Lys Arg

130 135 140

Pro Val Glu Gln Ser Pro Gln Glu Pro Asp Ser Ser Ser Gly Ile Gly

145 150 155 160

Lys Thr Gly Gln Gln Pro Ala Lys Lys Arg Leu Asn Phe Gly Gln Thr

165 170 175

Gly Asp Ser Glu Ser Val Pro Asp Pro Gln Pro Leu Gly Glu Pro Pro

180 185 190

Ala Thr Pro Ala Ala Val Gly Pro Thr Thr Met Ala Ser Gly Gly Gly

195 200 205

Ala Pro Met Ala Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Asn Ala

210 215 220

Ser Gly Asn Trp His Cys Asp Ser Thr Trp Leu Gly Asp Arg Val Ile

225 230 235 240

Thr Thr Ser Thr Arg Thr Trp Ala Leu Pro Thr Tyr Asn Asn His Leu

245 250 255

Tyr Lys Gln Ile Ser Ser Thr Ser Thr Gly Ala Ser Asn Asp Asn His

260 265 270

Tyr Phe Gly Tyr Gly Thr Pro Trp Gly Tyr Phe Asp Phe Asn Arg Phe

275 280 285

His Cys His Phe Ser Pro Arg Asp Trp Gln Arg Leu Ile Asn Asn Asn

290 295 300

Trp Gly Phe Arg Pro Lys Arg Leu Asn Phe Lys Leu Phe Asn Ile Gln

305 310 315 320

Val Glu Glu Val Thr Thr Asn Asp Gly Val Thr Thr Ile Ala Asn Asn

325 330 335

Leu Thr Ser Thr Val Gln Val Phe Ser Asp Ser Glu Tyr Gln Leu Pro

340 345 350

Tyr Val Leu Gly Ser Ala His Gln Gly Cys Leu Pro Pro Phe Pro Ala

355 360 365

Asp Val Phe Met Ile Pro Gln Tyr Gly Tyr Leu Thr Leu Asn Asn Gly

370 375 380

Ser Gln Ala Val Gly Arg Ser Ser Phe Tyr Cys Leu Glu Tyr Phe Pro

385 390 395 400

Ser Gln Met Leu Arg Thr Gly Asn Asn Phe Thr Phe Ser Tyr Thr Phe

405 410 415

Glu Glu Val Pro Phe His Ser Ser Tyr Ala His Ser Gln Ser Leu Asp

420 425 430

Arg Leu Met Asn Pro Leu Ile Asp Gln Tyr Leu Tyr Tyr Leu Asn Arg

435 440 445

Thr Gln Asn Gln Ser Gly Ser Ala Gln Asn Lys Asp Leu Leu Phe Ser

450 455 460

Arg Gly Ser Pro Ala Gly Met Ser Val Gln Pro Lys Asn Trp Leu Pro

465 470 475 480

Gly Pro Cys Tyr Arg Gln Gln Arg Val Ser Lys Thr Lys Thr Asp Asn

485 490 495

Asn Asn Ser Asn Phe Thr Trp Thr Gly Ala Ser Lys Tyr Asn Leu Asn

500 505 510

Gly Arg Glu Ser Ile Ile Asn Pro Gly Thr Ala Val Ala Ser His Lys

515 520 525

Asp Asp Glu Asp Lys Phe Phe Pro Met Ser Gly Val Met Ile Phe Gly

530 535 540

Lys Glu Ser Ala Gly Ala Ser Ser Thr Ala Leu Asp Asn Val Met Ile

545 550 555 560

Thr Asp Glu Glu Glu Ile Lys Ala Thr Asn Pro Val Ala Thr Glu Arg

565 570 575

Phe Gly Thr Val Ala Val Asn Phe Gln Ser Ser Ser Thr Asp Pro Ala

580 585 590

Thr Gly Asp Val His Ala Met Gly Ala Leu Pro Gly Met Val Trp Gln

595 600 605

Asp Arg Asp Val Tyr Leu Gln Gly Pro Ile Trp Ala Lys Ile Pro His

610 615 620

Thr Asp Gly His Phe His Pro Ser Pro Leu Met Gly Gly Phe Gly Leu

625 630 635 640

Lys Asn Pro Pro Pro Gln Ile Leu Ile Lys Asn Thr Pro Val Pro Ala

645 650 655

Asn Pro Pro Ala Glu Phe Ser Ala Thr Lys Phe Ala Ser Phe Ile Thr

660 665 670

Gln Tyr Ser Thr Gly Gln Val Ser Val Glu Ile Glu Trp Glu Leu Gln

675 680 685

Lys Glu Asn Ser Lys Arg Trp Asn Pro Glu Val Gln Tyr Thr Ser Asn

690 695 700

Tyr Ala Lys Ser Ala Asn Val Asp Phe Thr Val Asp Asn Asn Gly Leu

705 710 715 720

Tyr Thr Glu Pro Arg Pro Ile Gly Thr Arg Tyr Leu Thr Arg Pro Leu

725 730 735

Claims (32)

1. An adeno-associated virus (AAV) comprising an AAV capsid and a minigene having an AAV inverted terminal repeat and a heterologous gene operably linked to regulatory sequences which direct expression of the heterologous gene in a host cell, wherein the AAV capsid comprises an AAV vp1 protein, an AAV vp2 protein and an AAV vp3 protein, the AAV vp1 protein having i) a sequence consisting of amino acids 1 to 738 in SEQ ID No. 4(AAVrh46) and having a D41N modification, or ii) a sequence at least 95% identical to a sequence consisting of amino acids 1 to 738 in SEQ ID No. 4 and having a residue 41 of N (D41N).

2. An adeno-associated virus (AAV) comprising an AAV capsid and a minigene having an AAV inverted terminal repeat and a heterologous gene operably linked to regulatory sequences which direct expression of the heterologous gene in a host cell, wherein the AAV capsid comprises an AAV vp1 protein, an AAV vp2 protein and an AAV vp3 protein, the AAV vp1 protein having i) a sequence consisting of amino acids 1 to 738 in SEQ ID No. 4(AAVrh46) and having a modification of G135P, or ii) a sequence at least 95% identical to a sequence consisting of amino acids 1 to 738 in SEQ ID No. 4 and having residue 135 of P (G135P).

3. An adeno-associated virus (AAV) comprising an AAV capsid and a minigene having an AAV inverted terminal repeat and a heterologous gene operably linked to regulatory sequences which direct expression of the heterologous gene in a host cell, wherein the AAV capsid comprises an AAV vp1 protein, an AAV vp2 protein and an AAV vp3 protein, the AAV vp1 protein having i) a sequence consisting of amino acids 1 to 738 in SEQ ID No. 4(AAVrh46) and having a modification of a136V, or ii) a sequence at least 95% identical to a sequence consisting of amino acids 1 to 738 in SEQ ID No. 4 and having residue 136V (a 136V).

4. The AAV of claim 1, wherein the AAV inverted terminal repeat is from a different AAV than the AAV providing the capsid protein.

5. A composition comprising the AAV of claim 1 and a physiologically compatible carrier.

6. The AAV of claim 1, wherein the heterologous gene encodes ornithine transcarbamylase, arginosuccinate synthase, arginosuccinate lyase, arginase, fumarylacetoacetate hydrolase, carbamyl phosphate synthase I, phenylalanine hydroxylase, alpha-1 antitrypsin, glucose-6-phosphatase, porphobilinogen deaminase, cystathionine beta-synthase, branched ketoacid decarboxylase, isovaleryl-CoA dehydrogenase, propionyl-CoA carboxylase, methylmalonyl-CoA mutase, glutaryl-CoA dehydrogenase (GCDH), beta-glucosidase, pyruvate carboxylate, liver phosphorylase, phosphorylase kinase, beta-Glucuronidase (GUSB), glycine decarboxylase, Low Density Lipoprotein (LDL) receptor, High Density Lipoprotein (HDL) receptor, beta-glucosidase, or a pharmaceutically acceptable salt thereof, A Very Low Density Lipoprotein (VLDL) receptor, scavenger receptor, glucocorticoid receptor, estrogen receptor, vitamin D receptor, nuclear receptor, cystic fibrosis transmembrane conductance regulator (CFTR) sequence, factor IX or a variant thereof, factor VIII or a variant thereof, an dystrophin gene product, or an immunoglobulin.

7. The AAV of claim 6, wherein the dystrophin gene product is a mini-dystrophin or a micro-dystrophin.

8. The AAV of claim 6, wherein the immunoglobulin comprises an IgG, IgM, IgA, IgD, IgE, chimeric immunoglobulin, humanized antibody and/or single chain antibody.

9. A recombinant nucleic acid molecule encoding the AAV vp1 protein of claim 1.

10. A cultured host cell comprising the nucleic acid molecule of claim 9.

11. The cultured host cell of claim 10 further comprising a rep gene.

12. The cultured host cell of claim 10, wherein the recombinant nucleic acid molecule is a plasmid.

13. The AAV of claim 2, wherein the AAV inverted terminal repeat is from a different AAV than the AAV providing the capsid protein.

14. A composition comprising the AAV of claim 2 and a physiologically compatible carrier.

15. The AAV of claim 2, wherein the heterologous gene encodes ornithine transcarbamylase, arginosuccinate synthase, arginosuccinate lyase, arginase, fumarylacetoacetate hydrolase, carbamyl phosphate synthase I, phenylalanine hydroxylase, alpha-1 antitrypsin, glucose-6-phosphatase, porphobilinogen deaminase, cystathionine beta-synthase, branched ketoacid decarboxylase, isovaleryl-CoA dehydrogenase, propionyl-CoA carboxylase, methylmalonyl-CoA mutase, glutaryl-CoA dehydrogenase (GCDH), beta-glucosidase, pyruvate carboxylate, liver phosphorylase, phosphorylase kinase, beta-Glucuronidase (GUSB), glycine decarboxylase, Low Density Lipoprotein (LDL) receptor, High Density Lipoprotein (HDL) receptor, beta-glucosidase, or a pharmaceutically acceptable salt thereof, A Very Low Density Lipoprotein (VLDL) receptor, scavenger receptor, glucocorticoid receptor, estrogen receptor, vitamin D receptor, nuclear receptor, cystic fibrosis transmembrane conductance regulator (CFTR) sequence, factor IX or a variant thereof, factor VIII or a variant thereof, an dystrophin gene product, or an immunoglobulin.

16. The AAV5 of claim 15, wherein the dystrophin gene product is a mini-dystrophin or a micro-dystrophin.

17. The AAV5 of claim 15, wherein the immunoglobulin comprises an IgG, IgM, IgA, IgD, IgE, a chimeric immunoglobulin, a humanized antibody, and/or a single chain antibody.

18. A recombinant nucleic acid molecule encoding the AAV vp1 protein of claim 2.

19. A cultured host cell comprising the nucleic acid molecule of claim 18.

20. The cultured host cell of claim 19 further comprising a rep gene.

21. The cultured host cell of claim 19, wherein the recombinant nucleic acid molecule is a plasmid.

22. The AAV of claim 3, wherein the AAV inverted terminal repeat is from a different AAV from the AAV providing the capsid protein.

23. A composition comprising the AAV of claim 3 and a physiologically compatible carrier.

24. The AAV of claim 3, wherein the heterologous gene encodes ornithine transcarbamylase, arginosuccinate synthase, arginosuccinate lyase, arginase, fumarylacetoacetate hydrolase, carbamyl phosphate synthase I, phenylalanine hydroxylase, alpha-1 antitrypsin, glucose-6-phosphatase, porphobilinogen deaminase, cystathionine beta-synthase, branched ketoacid decarboxylase, isovaleryl-CoA dehydrogenase, propionyl-CoA carboxylase, methylmalonyl CoA mutase, glutaryl-CoA dehydrogenase (GCDH), beta-glucosidase, pyruvate carboxylate, liver phosphorylase, phosphorylase kinase, beta-Glucuronidase (GUSB), glycine decarboxylase, Low Density Lipoprotein (LDL) receptor, High Density Lipoprotein (HDL) receptor, A Very Low Density Lipoprotein (VLDL) receptor, scavenger receptor, glucocorticoid receptor, estrogen receptor, vitamin D receptor, nuclear receptor, cystic fibrosis transmembrane conductance regulator (CFTR) sequence, factor IX or a variant thereof, factor VIII or a variant thereof, an dystrophin gene product, or an immunoglobulin.

25. The AAV of claim 24, wherein the dystrophin gene product is a mini-dystrophin or a micro-dystrophin.

26. The AAV of claim 24, wherein the immunoglobulin comprises IgG, IgM, IgA, IgD, IgE, a chimeric immunoglobulin, a humanized antibody and/or a single chain antibody.

27. A recombinant nucleic acid molecule encoding the AAV vp1 protein of claim 3.

28. A cultured host cell comprising the nucleic acid molecule of claim 27.

29. The cultured host cell of claim 28 further comprising a rep gene.

30. The cultured host cell of claim 28, wherein the recombinant nucleic acid molecule is a plasmid.

31. An adeno-associated virus (AAV) vector having a modified AAVrh48 capsid (rh48.2) having a modified amino acid sequence shown in SEQ ID NO:44 wherein the amino acid residue at position 304 is changed from proto-amino acid to asparagine.

32. An adeno-associated virus (AAV) vector having an AAVhu48 capsid selected from the group consisting of: (a) the hu48 capsid having an amino acid sequence shown in modified SEQ ID No. 50 wherein the original glycine at amino acid residue position 277 is changed to serine, the original glutamic acid at amino acid residue position 322 is changed to lysine, and the proto-amino acid at amino acid residue position 552 is changed to asparagine; and (b) the capsid of hu48 having the amino acid sequence shown in modified SEQ ID NO 50 in which the original glycine at amino acid residue position 277 is changed to serine and the original glutamic acid at amino acid residue position 322 is changed to lysine.

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